At Seattle Cancer Care Alliance, our specialists provide expert diagnosis and treatment of blood and bone marrow disorders. Leaders in bone marrow transplant and cellular immunotherapy, we offer innovative, FDA-approved treatments that save lives and leading-edge clinical trials.

On December 7-10, the American Society of Hematology (ASH) will host its 61st annual meeting, showcasing important scientific insights from around the world. More than 50 world-class specialists, many whom treat patients at Seattle Cancer Care Alliance (SCCA), will be presenting their pioneering research. Visit us at exhibit booth 2449 through Monday, December 10. 

Forty years ago, SCCA’s partner organization, Fred Hutch, pioneered the clinical use of bone marrow and stem cell transplantation. Since then, SCCA has been a leader in turning scientific discovery into exciting new treatments that are changing the way cancer is treated.

Highlighted Abstracts and Schedule
Our leading physician researchers will present oral abstracts and published data throughout the conference.

The Role of Antibody Binding Capacity in Bcma CAR-T Cell Therapy for Multiple Myeloma
Damian J. Green, MD
Friday Scientific Workshops
W240BCD (Orange County Convention Center)

Chimeric Antigen Receptor T Cell Therapy for PCD With an Emphasis on Multiple Myeloma

Hit the Ground Running: What You Need to Know About CAR T-Cell Therapy
David G. Maloney, MD
Friday Satellite Symposia
Regency T-V (Hyatt Regency Orlando)

This live symposium will prepare the hematologists/oncologists in attendance with the knowledge needed to understand and analyze all of the data on CAR T-cell therapy that will be presented during the 2019 ASH annual meeting. Experts on CAR T-cell therapy will discuss the basics of this therapy, clinical trial data for approved and emerging CAR T-cell products, and best practices for managing therapy-related adverse events. During the symposium, faculty will highlight must-see upcoming ASH presentations and posters, highlights of new key data and review of pivotal trials, and practical information about how to identify eligible patients and when to refer to a specialty center.

Management of Sickle Cell Disease Complications Beyond Acute Chest
Oyebimpe O. Adesina, MD, MS
Oral
Hall E2, Level 2 (Orange County Convention Center)

Education Program

Soluble C5b-9 As a Prognostic Biomarker for Thrombotic Microangiopathy at the Onset of Graft-Versus-Host Disease
Ang Li, MD
Oral
Session 721
Valencia BC (W415BC), Level 4 (Orange County Convention Center)

Thrombotic microangiopathy (TMA) is a known complication of allogeneic hematopoietic cell transplantation (HCT). Though the presence of graft-versus-host disease (GVHD) predicts the development of TMA, only a small subset of patients with GVHD will develop this condition. In the current study, we examined soluble C5b-9 (sC5b9), the terminal complement complex, as a potential biomarker for the development of TMA among patients with active GVHD.

The US Experience with Generic Imatinib in CML: Did Cost Predictions Meet Reality?
Gary H. Lyman, MD, MPH
Oral
W315, Level 3

Education Program

No Engraftment Advantage after Single or Double Umbilical Cord Blood Transplant (CBT) with the Addition of a Non-HLA Matched Off-the-Shelf Expanded Cord Blood Unit Compared to Conventional CBT: Results of a Randomized Trial
Filippo Milano, MD, PhD
Oral
Session 732
W307, Level 3 (Orange County Convention Center)

Based on pilot study data demonstrating safety and excellent survival [Blood 2014 124:46] in acute leukemia patients undergoing myeloablative cord blood transplant (CBT) plus infusion of an off-the-shelf non-HLA matched expanded CB unit (OTS) for bridging hematopoiesis, a randomized trial was conducted to determine whether myeloablative CBT with or without an OTS would confer more rapid neutrophil (ANC) engraftment and therefore a survival advantage.

Response to Sorafenib in FLT3/ITD AML Is Depedent on Co-Occurring Mutational Profile
Katherine G. Tarlock, MD
Oral
Session 615
W304, Level 3 (Orange County Convention Center)

FLT3/ITD mutations are among the most common in AML and are associated with adverse outcome. The addition of FLT3 inhibitors (FLT3-I) to cytotoxic therapy has provided improvements in outcome. We have previously shown that co-occurring mutations impact the clinical implications of FLT3/ITD, where those with NUP98-NSD1 fusions and/or WT1 mutations do particularly poorly (Figure 1A), regardless of ITD allelic ratio (AR). FLT3-I act on mutated and aberrantly activated FLT3, thus may be most effective in AML that is primarily driven by overactive FLT3 signaling. Given the significant overlap between FLT3/ITD and WT1 and NUP98-NSD1, we questioned whether response to FLT3-I may be modulated by these co-occurring variants.

Factors Associated with Response, CAR-T Cell In Vivo Expansion, and Progression-Free Survival after Repeat Infusions of CD19 CAR-T CellsClinically Relevant Abstract
Evandro D. Bezerra, MD
Oral
Session 704
Valencia A (W415A), Level 4 (Orange County Convention Center)

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR)-T cell immunotherapy has shown promising efficacy in patients with relapsed or refractory (R/R) B-cell malignancies. The potential benefits of repeat infusions of CD19 CAR-T cells are unknown, and the factors associated with response, CAR-T cell in vivo expansion, and progression-free survival (PFS) after repeat infusion of CD19 CAR-T cells have not been investigated.

Efficacy and Safety of Fully Human Bcma CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase Bcma Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma
Andrew J. Cowan, MD
Oral
Session 704
Valencia A (W415A), Level 4 (Orange County Convention Center)

Although the median survival for patients with multiple myeloma has improved dramatically, almost all patients will eventually relapse and become resistant to standard therapies. Chimeric antigen receptor T cells (CAR T cells) targeting B cell maturation antigen (BCMA) have shown early promise in MM, with high initial response rates. Responses are often incomplete and durability has been a key concern, with most patients relapsing within 1 year (Raje N et al NEJM 2019). We have previously demonstrated that gamma secretase inhibitors (GSI) increase BCMA surface density, decrease soluble BCMA levels and augment anti-tumor efficacy of BCMA CAR T cells in preclinical models. In a phase I first-in-human trial (NCT03502577), we combined CAR T cells expressing a fully human BCMA scFv with an orally administered gamma secretase inhibitor (JSMD194).

The US Experience with Generic Imatinib in CML: Did Cost Predictions Meet Reality?
Gary H. Lyman, MD, MPH
Oral
Sunburst Room (W340)

Education Program

Indolent Lymphomas: The Marathon Has a New Course
Ajay K. Gopal, MD
Oral
Tangerine 1 (WF1), Level 2 (Orange County Convention Center)

The treatment of indolent B cell non-Hodgkin lymphoma has evolved beyond the sequencing of multiple lines of combination chemotherapy. This session will focus on new strategies for these diseases, including new ways to target CD20, existing and new targeted therapies and combinations, and new immunotherapeutic approaches and tumor antigens. Lastly, we will review where autologous and allogeneic stem cell transplantation fit amidst these increasing treatment options.

223 Novel CD19t T-Antigen Presenting Cells Expand CD19 CAR T Cells In Vivo
Colleen E. Annesley, MD
Oral
Session 614
Tangerine 3 (WF3-4), Level 2 (Orange County Convention Center)

While immunotherapy with CD19 specific CAR T cells for relapsed/refractory (R/R) B-ALL achieves MRD negative remission in nearly all patients, relapse occurs in approximately half of patients and is frequently associated with early loss of CAR T cell persistence. Low CD19 antigen burden in the bone marrow prior to lymphodepletion and rapid contraction of CAR T cells in the blood after engraftment are predictive of early loss of CAR T cell persistence. We hypothesize that episodic antigen exposure using CD19t T cell antigen presenting cells (T-APCs) can trigger CD19 CAR T cell proliferation and re-activation in vivo, resulting in more durable CAR T cell persistence and diminished risk of CD19+ relapse. Here we report our experience to date using T-APCs following CD19 CAR T cell therapy for children and young adults with R/R B-ALL on clinical trial PLAT-03 (NCT03186118).

Additional Cytotoxic Chemotherapy Is Unlikely to Eliminate Measurable Residual Acute Myeloid Leukemia (AML)
Jacob Appelbaum, MD, PhD
Oral
Session 732
W307, Level 3 (Orange County Convention Center)

Measurable residual disease (MRD) following intensive induction chemotherapy for AML is associated with a high risk of relapse and shortened survival even after allogeneic hematopoietic stem cell transplantation (HSCT). Thus, it may be advisable to give additional chemotherapy to reduce or eradicate MRD prior to HSCT. However, this may expose patients to additional toxicity and delay HSCT. We used our institutional database to examine how often additional chemotherapy eliminated MRD and compared survival among patients with MRD according to whether they next received additional chemotherapy or allogeneic HSCT.

Machine Learning for Precision Medicine in Acute Myeloid Leukemia
Pamela S. Becker, MD, PhD
Special Scientific Symposia
Hall D, Level 2 (Orange County Convention Center)

Machine Learning (ML) is an application of artificial intelligence that has permitted interpretation of big data to assist in diagnosis, prediction of prognosis or selection of therapy for medical disorders. In the case of acute myeloid leukemia (AML), machine learning has previously been applied to several aspects, including 1) recognition of gene, cytogenetic, or microRNA signatures that predict response to therapy or overall prognosis, 2) prediction of new targeted inhibitors, and 3) development of a prediction model for mortality after allogeneic transplant. 

Increasing Lengths of First Complete Remission with 7+3 Induction Chemotherapy for Acute Myeloid Leukemia over the Past Four Decades: Analysis of SWOG Trial Data
Megan Othus, PhD
Oral
Session 613
W304, Level 3 (Orange County Convention Center)

We have previously shown that the survival of patients with AML who fail to achieve complete remission (CR) with 7+3 has improved since the 1980s. However, although CR rates with 7+3 have improved over the last four decades, we have not previously evaluated how outcomes for patients who achieve a CR1 with 7+3 has changed over time. Here we evaluate if either length of first CR (CR1) after 7+3 or of survival after relapse from CR1 has changed over the last four decades.

Comparative Analysis of Total Body Irradiation (TBI)-Based and Non-TBI-Based Myeloablative Conditioning for Acute Myeloid Leukemia in Remission with and without Measurable Residual DiseaseClinically Relevant Abstract
Evandro D. Bezerra, MD
Oral
Session 732
W307, Level 3 (Orange County Convention Center)

Myeloablative allogeneic hematopoietic cell transplantation (HCT) is a common post-remission treatment strategy for medically fit adults with acute myeloid leukemia (AML) in morphologic remission. Several conditioning regimens have been utilized for this purpose, with ongoing controversy regarding the benefit of high-dose total body irradiation (TBI) in this setting. It is also unknown whether the relative value of TBI- versus non-TBI-based myeloablative conditioning differs for patients presenting with measurable residual disease (MRD) at the time of HCT from those in MRDnegremission. These open questions prompted us to compare outcomes among a large cohort of adult AML patients in MRDposand MRDnegremission who had myeloablative allogeneic HCT at our institution.

CBFA2T3-GLIS2 induces Malignant Transformation of Primitive CD34+ Cord Blood Cells and Recapitulates Infant Megakaryocytic Leukemia
Tiffany A. Hylkema, BS
Poster
Session 617
Hall B, Level 2

CBFA2T3-GLIS2 fusions are uniquely expressed in infants with AML and its presence is associated with refractory disease with high induction failure and nearly uniform fatality. Recent studies into varying features of this refractory leukemia have defined a unique immunophenotype that is referred to as the RAM phenotype with exceptionally high CD56 expression. Further, deep sequencing of patients with this fusion has failed to identify additional recurrent sequence or structural variants, suggesting that the presence of this fusion might be sufficient for malignant transformation. Given its presence uniquely in infants and lack of cooperating events, the premise of malignant transformation by a single, highly penetrant event might be justified. Despite discovery efforts to define genes, pathways, and networks that are dysregulated in this AML subset, lack of appropriate model systems has limited pre-clinical evaluation of potential therapies. Prior efforts in generating cell lines and xenograft models have met with limited success. We inquired whether primitive CD34+ cord blood cells might provide the appropriate developmental milieu to study fusion-induced transformation.

Patterns and Predictors of Emicizumab Adherence in People with Hemophilia
Ang Li, MD
Poster
Session 904
Hall B, Level 2 (Orange County Convention Center)

Emicizumab is a subcutaneously administered, humanized bispecific monoclonal antibody that is recently approved for hemostatic prophylaxis in people with hemophilia A (PWH) with or without factor VIII inhibitors. We hypothesize that the new route and frequency of administration would lead to better treatment adherence compared to factor or bypass products in PWH outside of clinical trials. We performed the current study to test the hypothesis and to examine potential predictors of non-adherence associated with emicizumab treatment.

Treatment of Refractory Acute Myeloid Leukemia and High-Grade Myelodysplastic Syndrome: Implications of Further Care at an Academic Center Versus Community Setting
Noam E. Kopmar, MD
Poster
Session 906
Hall B, Level 2 (Orange County Convention Center)

Many patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome with 10-19% blasts (MDS-EB2) do not enter complete remission (CR) following initial induction chemotherapy. At an academic referral center, such patients often stay to receive additional treatment, or return to their home communities for further care. For patients and providers alike, the decision about whether to stay or go after initial treatment failure is often fraught. To better inform such decision-making, in this retrospective single-center analysis, we compared covariate-adjusted survival for patients who elected to stay for further treatment at our center and those who returned to their home communities for subsequent care.

Veneto-STOP Study: Sequential Assessment of Minimal Residual Disease By Next Generation Sequencing to Optimize Outcomes and Minimize Exposure in Venetoclax-Treated CLL Patients
Chaitra S. Ujjani, MD
Poster
Session 642
Hall B, Level 2 (Orange County Convention Center)

The treatment indications for venetoclax in CLL are broadening quickly. While the initial approval was for relapsed patients with del 17p (Stilgenbauer S, et al. JCO 2018), it has subsequently been extended to all patients (Seymour J, et al. NEJM 2018, Fischer K, et al. NEJM 2019). The duration of therapy with each approval has evolved as well, from continuing therapy until progression/toxicity to 1 year in front-line CLL. The limited durations of therapy were applied to all patients based on trial design and were not dependent on response to treatment.

Undetectable minimal residual disease (U-MRD) with venetoclax is associated with improved progression-free survival (PFS), both as a single agent and in combination with rituximab (Stilgenbauer S, et al. JCO 2018, Seymour J, et al. NEJM 2018). Early phase data suggest that patients who discontinue venetoclax after achieving MRD negativity can be monitored off therapy and successfully retreated upon relapse (Seymour J, et al, Lancet Onc 2017). However, patients who discontinue therapy with persistent residual disease have a higher incidence of relapse (Kater A, et al. JCO 2019).

Together, these data suggest that the duration of venetoclax therapy should be individualized, based on the depth of response one achieves and not a fixed duration schedule. Therefore, we propose a prospective clinical trial, utilizing MRD assessment with a next generation sequencing (clonoSEQ®) assay to guide clinical decision making in patients with CLL receiving venetoclax-based regimens.

Comparative Analysis of Patterns of Infectious Complications of Outpatient Vs. Inpatient Care Following Intensive Induction Chemotherapy for Adults with Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid NeoplasmsClinically Relevant Abstract
Anna B. Halpern, MD
Poster
Session 613
Hall B, Level 2 (Orange County Convention Center)

Because infections are a major cause of morbidity and mortality after AML induction chemotherapy, patients typically remain hospitalized for monitoring and rapid antimicrobial therapy until hematopoietic recovery. With declining early mortality and improved oral antimicrobials, interest in moving post-induction care to the outpatient setting has emerged. In the 5-year period since completing a prospective phase 2 trial evaluating an Early Hospital Discharge (EHD) strategy, EHD following AML-like induction chemotherapy has become routine at our institution. In recent retrospective analyses, we found >80% of EHD patients required hospital readmission, primarily for neutropenic fever. Still, the EHD strategy was safe and reduced healthcare resource utilization, and EHD patients spent >70% of their post-chemotherapy time as outpatients. Here, we investigated differences in the pattern of infectious complications between patients managed as outpatients following induction chemotherapy and those who remain hospitalized until hematopoietic recovery.

High Throughput Drug Synergy Testing in a Clinical Trial of Panobinostat, Carfilzomib, Dexamethasone to Define Response Biomarkers for Relapsed/Refractory Multiple Myeloma
Pamela S. Becker, MD, PhD
Poster
Session 653
Hall B, Level 2 (Orange County Convention Center)

The treatment of multiple myeloma (MM) is optimized by use of combination regimens consisting of agents with different mechanisms of action. Panobinostat is a pan-inhibitor of histone deacetylases types I,II, and IV. Panobinostat, bortezomib, dexamethasone was shown to be an effective regimen (San Miguel et al Lancet Hematol 2016; Richardson et al Blood 2016), leading to the FDA approval of panobinostat for patients with relapsed/refractory MM. Carfilzomib is a proteasome inhibitor that was FDA approved in relapsed/refractory MM with the advantage of minimal neuropathy. Panobinostat and carfilzomib has also been shown to be a highly active regimen in relapsed/refractory MM with an overall response rate of up to 75% (Berdeja et al, Haematologica, 2015). With the heterogeneity of MM, individual patients exhibit wide variability in responses to drug combinations. A test that could predict patient responses to specific agents might enable clinicians to optimize therapy for patients, improving outcomes. We developed an in vitro high throughput drug sensitivity assay with formal synergy testing to predict response. In this ongoing trial, Panobinostat with Carfilzomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Correlation with In Vitro Chemosensitivity Testing (NCT03256045), we will correlate individual patient in vitro sensitivity assay results with individual clinical response to the same triple drug regimen.

Response to Bcma CAR-T Cells Correlates with Pretreatment Target Antigen Density and Is Improved By Small Molecule Inhibition of Gamma Secretase
Damian J. Green, MD
Poster
Session 653
Hall B, Level 2 (Orange County Convention Center)

The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in multiple myeloma [MM], however durable responses remain elusive and most studies report >50% of patients relapsing within 18 months of receiving CAR-T cell therapy. The mechanism of relapse is likely the consequence of multiple factors including the variable distribution of BCMA on tumor cells, allowing cells with low antigen density to escape. Initial target density, receptor downregulation and the emergence of antigen loss variants have all been implicated in relapse following CAR-T cells directed against CD22 and CD19. Reduced or absent BCMA expression may similarly be linked to relapse in MM. We have previously demonstrated that BCMA cleavage by the γ-secretase complex reduces ligand density for CAR-T cell recognition, and that a small molecule γ-secretase inhibitor (GSI) markedly increases surface BCMA levels in a dose-dependent fashion while improving CAR-T cell recognition in preclinical models.

Comparison of Outcomes After Early Hospital Discharge (EHD) Following Intensive Induction Vs Post-Remission Chemotherapy for Adults With Acute Myeloid Leukemia (AML) And Other High-Grade Myeloid Neoplasms
Anna B. Halpern, MD
Poster
Session 613
Hall B, Level 2 (Orange County Convention Center)

An international survey we recently conducted indicated that, even today, adults with acute myeloid leukemia (AML) standardly remain hospitalized after completion of induction chemotherapy until resolution of cytopenias due to a high risk of infection and frequent need for transfusions. In contrast, over the last five years at our institution, hospital discharge immediately following completion of induction chemotherapy has become routine after a phase 2 trial evaluating an Early Hospital Discharge (EHD) strategy showed this approach to be safe and cost-effective. On the other hand, EHD is a nearly-universal practice following post-remission or “consolidation” therapy. Here, we sought to compare safety and healthcare resource utilization outcomes for patients who are discharged to the outpatient setting following intensive induction vs. consolidation chemotherapy.

Diffuse Large B-Cell Lymphoma is Infiltrated with Functional CD8+ T-cells Lacking the Hallmarks of Exhaustion
Adam Greenbaum, MD
Poster
Session 622
Hall B, Level 2 (Orange County Convention Center)

B-cell non-Hodgkin lymphomas (NHL) are hematologic malignancies that arise in the lymph node but are not cleared by the immune cells present. The failure of anti-tumor immunity may be due to immune checkpoints such as the PD-1/PD-L1 axis, which can cause T-cell exhaustion. In contrast to Hodgkin lymphoma, checkpoint blockade in NHL has showed limited efficacy. Here we demonstrate that T-cells in DLBCL do not exhibit an exhausted phenotype which may explain the poor response to immune checkpoint inhibitors.

A Multi-Omic Precision Medicine Clinical Trial in Acute Leukemia
Pamela S. Becker, MD, PhD
Poster
Session 604
Hall B, Level 2 (Orange County Convention Center)

Conventional precision medicine for cancer targets specific gene mutations, but single agent inhibitors rarely result in remission or improve survival in acute leukemia. Current functional screening strategies assay individual drugs, thus missing potential synergistic combinations. We therefore developed a multi-omic approach that integrates mutation data, gene expression data (transcriptome), and in vitro drug sensitivity (functional) data to select drugs including drug combinations for individual patients. Herein we report results of the clinical trial testing this concept [NCT02551718]. This study contributed to validation of 44 genes identified for which expression correlates with drug sensitivity (Lee S-I et al. Nat Commun 2018).

Ibrutinib in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma: Final Results from a Prospective Phase II Study
Solomon A. Graf, MD
Poster
Session 626
Hall B, Level 2 (Orange County Convention Center)

Relapsed or refractory (R/R) transformed indolent B-cell non-Hodgkin lymphoma (iB-NHL) is an uncommon clinical entity associated with poor prognosis. Unfortunately, most trials of aggressive B-NHL tend to specifically exclude transformed disease resulting in scant prospective data to guide therapy. We performed a prospective phase II trial of single agent ibrutinib in patients with previously treated transformed iB-NHL and now report the final results (NCT02207062).

High-Throughput Functional Drug Screening and Genomic Analysis to Guide Individualized Therapy for Relapsed/Refractory Multiple Myeloma
David G. Coffey, MD
Session 653
Hall B, Level 2 (Orange County Convention Center)

The response to treatment for patients with relapsed/refractory multiple myeloma (MM) is highly variable. This may in part be related to the broad genomic heterogeneity that has been reported across individual patients. We hypothesize that in vitro functional drug screening and correlated genomic analyses of patient tumor cells is feasible and may improve clinical treatment response. To address this, we developed a custom high-throughput drug sensitivity (HTS) assay enabling simultaneous testing of 170 chemotherapy drugs and targeted inhibitors, as well as correlative gene expression and mutational analysis by next-generation sequencing. We report on the feasibility of this approach in a clinical trial enrolling patients with relapsed/refractory MM (NCT03389347).

Mini- vs. Regular-Dose CLAG-M (Cladribine, Cytarabine, G-CSF, and Mitoxantrone) in Medically Less Fit Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) and Other High-Grade Myeloid Neoplasms
Anna B. Halpern, MD
Poster
Session 615
Hall B, Level 2 (Orange County Convention Center)

Optimal treatment for medically less fit adults with acute myeloid leukemia (AML) remains uncertain. Retrospective data suggest intensive therapy may lead to better outcomes in these patients. However, these findings must be interpreted cautiously because of the possibility of selection bias and other confounders. Ideally, the optimal treatment intensity is defined via randomized trial but whether patients and their physicians are amenable to such a study is unknown. We therefore designed a trial (NCT03012672) to 1) evaluate the feasibility of randomization between intensive and non-intensive therapy in this population and 2) examine the impact of treatment intensity on response rate and survival. We used CLAG-M as high-dose cytarabine-based intensive induction therapy. Rather than selecting different classes of drugs in the 2 treatment arms– which may have different modes of action and therefore confound the question of treatment intensity – we used reduced-dose (“mini”) CLAG-M as the non-intensive comparator.

CLL: Therapy, excluding Transplantation: Combination and Novel Treatment
Mazyar Shadman, MD, MPH
Oral
Session 642
Orange County Convention Center, Hall E1

Moderators: Sameer A. Parikh, MD, Mayo Clinic and Mazyar Shadman, MD, Uw/Fred Hutchinson Cancer Research Center

Sirolimus Combined with Cyclosporine (CSP) and Mycophenolate Mofetil (MMF) As Graft-Vs-Host Disease (GVHD) Prophylaxis after Nonmyeloablative (NMA) Hematopoietic Cell Transplantation (HCT) Using HLA Class I or Class II Antigen Mismatched Donors
Brenda M. Sandmaier, MD
Oral
Session 722
W230, Level 2 (Orange County Convention Center)

The success of HCT is highly dependent on the availability of compatible donors. Depending on ethnicity, fully HLA-matched donors cannot be identified for 25–84% of patients. In an effort to extend the use of HLA-mismatched donors to patients only eligible for NMA HCT, we previously demonstrated that engraftment and long-term survival can be achieved using CSP and MMF immunosuppression after HLA class I antigen-mismatched HCT (Nakamae et al, 2010). Based on this trial, we designed a phase II multi-center trial to assess the efficacy of GVHD prophylaxis with triple immune suppression with CSP, MMF and sirolimus after HLA class I or class II antigen mismatched NMA HCT (fludarabine 90mg/m2 and 2–3 Gy TBI). Patients ineligible for high-dose conditioning with only HLA class I or class II antigen mismatched donors available were eligible for inclusion. The primary objective was to determine whether the incidence of grades 2-4 acute GVHD can be reduced to less than the historical rate of 70% with the triple-immunosuppression. The evaluation was planned to be carried out separately among HLA class I and class II mismatched patients. Secondary objectives included day 100 non-relapse mortality (NRM) and grades 3-4 acute GVHD. CSP was started on day -3 and continued to day +150 and then tapered off by day +180. Sirolimus was started on day -3 through day +180 and then tapered off by day +365. MMF was given thrice daily from days 0 to +30 then twice daily to day +100 and tapered off by day +150. A total of 76 patients were enrolled and received conditioning with fludarabine and TBI followed by infusion of unmodified G-CSF mobilized peripheral blood stem cell (PBSC) grafts. The median age was 63 (21–76) years, and median follow-up of surviving patients was 47 (4–94) months. 51 (67%) and 25 (33%) of patients had HLA class I or II mismatches, respectively. Transplant demographics are summarized in Table 1.

Indolent Lymphomas: The Marathon Has a New Course
Ajay K. Gopal, MD
OCCC, Tangerine 1 (WF1)

The treatment of indolent B cell non-Hodgkin lymphoma has evolved beyond the sequencing of multiple lines of combination chemotherapy. This session will focus on new strategies for these diseases, including new ways to target CD20, existing and new targeted therapies and combinations, and new immunotherapeutic approaches and tumor antigens. Lastly, we will review where autologous and allogeneic stem cell transplantation fit amidst these increasing treatment options.

Indolent Lymphomas: The Marathon Has a New Course
Ajay K. Gopal, MD
Tangerine 1 (WF1), Level 2 (Orange County Convention Center)

The treatment of indolent B cell non-Hodgkin lymphoma has evolved beyond the sequencing of multiple lines of combination chemotherapy. This session will focus on new strategies for these diseases, including new ways to target CD20, existing and new targeted therapies and combinations, and new immunotherapeutic approaches and tumor antigens. Lastly, we will review where autologous and allogeneic stem cell transplantation fit amidst these increasing treatment options.

High Accuracy, Low-Cost Transcriptional Diagnostic to Transform Lymphoma Care in Low- and Middle-Income Countries
Edward Briercheck, MD, PhD
Session 902
W307, Level 3 (Orange County Convention Center)

The majority of people worldwide lack access to high accuracy diagnostics to guide lymphoma therapy. As a consequence, many patients receive incorrect or no treatment. We hypothesized that a low-cost, parsimonious gene expression assay using FFPE biopsies from low-income settings could distinguish multiple lymphoma subtypes. Accurate diagnoses would make it possible to extend high therapeutic index agents currently available within high-income countries to underserved patients around the world.

The Global State of Hematopoietic Stem Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation (WBMT) Database and the Global Burden of Disease Study
Andrew J. Cowan, MD
Oral
Session 902
Orange County Convention Center, W307

Multiple myeloma (MM), is a clonal plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. MM is a global disease – worldwide in 2016, there were 138509 incident cases with an age standardized incidence rate (ASIR) of 2.1 per 100 000 persons, with a 126% global increase in incident cases from 1990 to 2016 (Cowan AJ et al JAMA Oncology 2018). Access to effective care, including proteasome inhibitors, immunomodulatory agents, and autologous hematopoietic stem cell transplantation (HSCT) is largely limited to high-income sociodemographic index (SDI) countries. SCT remains the standard of care for eligible patients, and in general is more affordable and accessible worldwide than novel therapies. We sought to evaluate the rates and utilization of ASCT globally from 2006-2015 to better characterize access to SCT for patients with MM.

Low Achievement of End of Life Quality Measures in Large B-Cell Lymphoma Patients Who Progressed after CD19-Specific CAR-T Cell Therapy
Ryan C. Lynch, MD
Oral
Session 902
W307, Level 3 (Orange County Convention Center)

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is FDA-approved in patients with relapsed or refractory large B-cell lymphomas and can lead to long-term remissions in 35-40% of patients. Outcomes in patients who progress after CAR T-cell therapy is poor, with a median overall survival (OS) of 5.3 months with few long-term survivors (Chow et al. AJH 2019). Achieving quality end of life (EOL) care for patients with hematologic malignancies has been a challenge, and widespread consensus on what are acceptable metrics is lacking (Odejide et al JCO 2016). EOL care among large B-cell lymphoma patients who progressed after CAR-T cell therapy has not been previously examined.

Combination of NKTR-255, a Polymer Conjugated Human IL-15, with CD19 CAR T Cell Immunotherapy in a Preclinical Lymphoma Model
Cassie Chou, MD, PhD
Poster
Session 625
"Hall B, Level 2 (Orange County Convention Center) "

CD19 CAR T immunotherapy has been successful in achieving durable remissions in some patients with relapsed/refractory B cell lymphomas, but disease progression and loss of CAR T cell persistence remains problematic. Interleukin 15 (IL-15) is known to support T cell proliferation and survival, and therefore may enhance CAR T cell efficacy, however, utilizing native IL-15 is challenging due to its short half-life and poor tolerability in the clinical setting. NKTR-255 is a polymer-conjugated IL-15 that retains binding affinity to IL15Rα and exhibits reduced clearance, providing sustained pharmacodynamic responses. We investigated the effects of NKTR-255 on human CD19 CAR T cells both in vitro and in an in vivo xenogeneic B cell lymphoma model and found improved survival of lymphoma bearing mice receiving NKTR-255 and CAR T cells compared to CAR T cells alone. Here, we extend upon these findings to further characterize CAR T cells in vivo and examine potential mechanisms underlying improved anti-tumor efficacy.

Treatment Discontinuation Patterns for Patients with CLL in the Real-World Settings: Results from a Multi-Center Study
Mazyar Shadman, MD, MPH
Poster
Session 642
Hall B, Level 2

The recent approval of novel agents (NAs) has changed the treatment landscape in chronic lymphocytic leukemia (CLL), however, there remains uncertainty regarding treatment discontinuation patterns in real-world (RW) settings. This study assessed patterns of and reasons for discontinuation for patients (pts) treated with chemotherapy/chemoimmunotherapy (CT/CIT) and NAs in first (1L) and second (2L) lines of therapy in CLL.

Demonstration of the Safety of Post Induction Infusion of Ex-Vivo Expanded Cord Blood Progenitor Cells in Pediatric Patients with Relapsed/Refractory Acute Myelogenous Leukemia
Ann Dahlberg, MD
Poster
Session 613
Hall B, Level 2

AML therapy requires intensive and highly immunosuppressive cytotoxic therapy leading to prolonged neutropenia. Prolonged neutropenia leads to highly invasive bacterial and fungal infections causing high rates of infection related morbidity and mortality. Even with improved antimicrobial and antifungal therapy, infectious complications remain a common cause of treatment related morbidity and mortality. There is a large need for strategies to reduce the toxicity of AML therapy and infectious complications in particular. We proposed that post induction infusion of non HLA-matched, off-the-shelf (OTS) ex-vivo expanded cord blood progenitor cells may provide rapid, short term bridging hematopoiesis and truncated period of neutropenia. Here we describe results of a pilot study assessing the safety of infusing this OTS product following FLAG chemotherapy in pediatric patients.

CD20 Targeted Chimeric Antigen Receptor T-cells (CART) for Treatment of High-Risk B-Cell Non-Hodgkin Lymphomas (B-NHL)
Mazyar Shadman, MD, MPH
Poster
Session 704
Hall B, Level 2

Chimeric antigen receptor T-cells (CAR-T) targeting CD19 have shown clinical efficacy in high-risk B-cell lymphomas, which has led to approval of 2 such therapies (axicabtagene ciloleucel and tisagenlecleucel) for large B-cell lymphoma after 2 lines of treatment. Despite the promising results, complete remission (CR) is achieved in ~ 50% of patients, and with longer follow-up progression-free survival is around 40%. Therefore, finding effective treatments for high-risk B-NHLs remains an unmet need. CD20 is a proven therapeutic target for B-Cell Non-Hodgkin Lymphomas (B-NHL), supported by previously approved naked and radiolabeled anti-CD20 monoclonal antibodies and a number of studies investigating novel bispecific antibodies targeting this antigen. CD20-targeted CAR-T is another potential adoptive immunotherapy option that could be utilized in combination or sequentially before or after CD19 CAR-T, depending on efficacy. Here, we present our ongoing phase I/II clinical trial investigating safety and efficacy of CD20 CAR-T for high-risk B-NHLs (NCT03277729).

Myelodysplastic Syndrome with Excess Blasts and Secondary Acute Myeloid Leukemia: Same Disease with Different Blast Count
Xueyan Chen, MD, PhD
Poster
Session 617
Hall B, Level 2 (Orange County Convention Center)

The World Health Organization (WHO) diagnoses acute myeloid leukemia (AML) if ≥20% myeloid blasts are present in peripheral blood or bone marrow. Consequently a patient with even 19% blasts is often ineligible for an “AML study”. A less arbitrary means to define “AML” and myelodysplastic syndromes (“MDS”) emphasizes biologic features. Here, focusing on patients with WHO-defined MDS with excess (5-19%) blasts (MDS-EB) or AML with myelodysplasia-related changes (AML-MRC) or therapy-related (t-AML) (WHO defined secondary AML), we compared morphologic blast percentage (MBP) with the frequency of mutations in genes belonging to different functional groups, and with the variant allele frequency (VAF) for individually mutated genes.

Impact of Lab Abnormalities at the Time of Progression in Patients Receiving CD19-Specific CAR T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphomas
Ryan C. Lynch, MD
Poster
Session 627
Hall B, Level 2 (Orange County Convention Center)

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is FDA approved in patients with relapsed or refractory large B-cell lymphomas. While 35-40% of patients may achieve a durable complete response (CR), the toxicity incurred with CAR-T therapy could impact the ability to receive subsequent treatment in those who progress after CAR-T infusion. Our prior data suggested that patients who experienced early progression had inferior overall survival. We now update our results and evaluate the impact of laboratory abnormalities and comorbidities at the time of progression on overall survival.

Anti-Apoptotic BCL-2 Family Members Confer Resistance to Calicheamicin-Based Antibody-Drug Conjugate Therapy of Acute Leukemia
Colin Godwin, MD
Poster
Session 604
Hall B, Level 2 (Orange County Convention Center)

With gemtuzumab ozogamicin (GO; targeting CD33) and inotuzumab ozogamicin (IO; targeting CD22), 2 antibody-drug conjugates delivering a toxic calicheamicin (CLM) derivative have recently been approved for the treatment of people with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), respectively. While effective in some, many patients do not benefit from these ADCs. It is unclear to what degree anti-apoptotic BCL-2 family members are involved in modulating efficacy of CLM-based ADCs, with limited studies coming to differing conclusions. Given the clinical availability of small molecule inhibitors for BCL-2 family proteins (BCLi), here we clarify the impact of BCL-2 family proteins on the anti-leukemic activity of CLM-ADCs.

CD117 Expression Is Associated with Cytogenetic and Molecular Profiles and Outcome in Pediatric Acute Myeloid Leukemia
Katherine Tarlock, MD
Poster
Session 617
Hall B, Level 2 (Orange County Convention Center)

Cell surface antigen expression in AML is becoming focus of investigation as it relates to prognostic impact as well as potential therapeutic implications. The CD117 (c-KIT) receptor tyrosine kinase is expressed on the cell surface of hematopoietic stem cells and its signaling is important in cell survival, proliferation and differentiation. CD117 is expressed in a majority of AML cases. In addition, mutations in c-KIT have been identified in a subset of patients, specifically those with CBF AML (inv(16)/t(16;16) and t(8;21)). As there is increasing interest in using tyrosine kinase inhibitors with anti-KIT activity based on surface CD117 expression as treatment in AML, we sought to evaluate the association of CD117 expression with biologic and clinical features in pediatric and young adult (YA) AML.

Analyses of Predictors of Durable Treatment-Free Remission in Patients with Chronic Myeloid Leukemia in Chronic Phase Following Frontline or Second-Line Nilotinib
Jerald P. Radich, MD
Poster
Session 632
Hall B, Level 2 (Orange County Convention Center)

Some patients with chronic myeloid leukemia in chronic phase (CML-CP) who have a sustained deep molecular response (DMR) with tyrosine kinase inhibitors (TKIs) can discontinue therapy and achieve treatment-free remission (TFR). Thus far, no consistent variables that predict TFR have been identified. In long-term follow-up of patients who attempted TFR following front- or second-line nilotinib in the ENESTfreedom and ENESTop TFR studies, respectively, 192-week TFR rates were 44.2% (ENESTfreedom) and 46.0% (ENESTop), and adverse event rates tended to decrease over time during TFR. Previous analyses in ENESTfreedom suggested that lower Sokal risk score and consistent MR4.5 (BCR-ABL1 ≤ 0.0032% on the International Scale [IS]) in the consolidation phase were associated with maintaining TFR, whereas in ENESTop, a longer time in MR4.5 was associated with maintaining TFR. We sought to identify clinical predictors of a durable TFR by analyzing pooled data from ENESTfreedom and ENESTop.

Fully Closed, Large-Scale, and Clinical Grade Cell Sorting of Hematopoietic Stem Cell (HSC)-Enriched CD90+ Cells for Transplantation and Gene Therapy
Stefan Radtke, PhD
Poster
Session 711
Hall B, Level 2 (Orange County Convention Center)

Hematopoietic stem cell (HSC) gene therapy/editing is a viable treatment option for various hematological diseases and disorders including hemoglobinopathies and HIV/AIDS. Most if not all currently available approaches target CD34-enriched cell fractions, a heterogeneous mix of mostly committed progenitor cells and only very few true HSCs with long-term multilineage engraftment potential. As a consequence, gene therapy/editing approaches are currently limited in their HSC targeting efficiency, very expensive consuming huge quantities of modifying reagents, and can lead to unwanted side-effects in non-target cells.

We recently described a novel HSC-enriched CD34 subset (CD90+CD45RA-) that is exclusively responsible for rapid recovery onset, robust long-term multilineage engraftment, as well as entire reconstitution of the bone marrow stem cell compartment in the nonhuman primate (NHP) stem cell transplantation and gene therapy model (Radtke et al. 2017, STM). Most importantly, we demonstrate that this CD34 subset reduces the number of target cells, modifying reagents and costs by more than 10-fold without compromising the long-term efficiency of gene-modification in the NHP (Humbert and Radtke et al. 2019, STM). Here, we aimed to develop a clinical protocol to reliably purify and efficiently gene-modify human HSC-enriched CD90+ cell fractions.

Severe Cytokine Release Syndrome Is Associated with Impaired Hematopoietic Recovery after CD19-Targeted CAR-T Cell Therapy
Krishna Juluri, MD
Poster
Session 704
Hall B, Level 2 (Orange County Convention Center)

Chimeric antigen receptor therapy (CAR-T) directed against CD19 has demonstrated efficacy in patients with relapsed/refractory (R/R) B-cell malignancies. Delayed hematopoietic recovery with grade 3/4 neutropenia and thrombocytopenia, requiring extended growth factor administration or transfusions, has been observed in patients undergoing CAR-T cell therapy, although the factors influencing recovery are poorly understood. In this study, we performed multivariable analyses to identify factors associated with hematopoietic recovery in patients undergoing CD19 CAR-T cell therapy.

Long Non-Coding RNAs (lncRNAs) Are Highly Associated with Disease Characteristics and Outcome in Pediatric Acute Myeloid Leukemia – a COG and Tpaml Study
Jenny L. Smith
Poster
Session 617
Hall B, Level 2 (Orange County Convention Center)

Childhood AML is a heterogeneous hematologic disease with a multitude of subtypes characterized by varying morphology, structural alterations, and recurrent mutations. Such heterogeneity and staggering number of genomic and transcriptional alterations has precluded appropriate risk classification. We investigated the expression of long non-coding RNAs (lncRNA) in childhood AML and explored its potential utility for more precise risk characterization at diagnosis.

Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II
Derek L. Stirewalt, MD
Poster
Session 617
Hall B, Level 2 (Orange County Convention Center)

ELN-2017 guideline is the gold standard for risk stratifying AML patients. However, clinical prognostic factors such as age are not incorporated into the guideline. Therefore, we examined if novel prognostic models incorporating clinical factors and expression of select transcripts can improve the current guideline. The prognostic models were developed utilizing molecular data from unsorted mononuclear cells (MNCs) and viable leukemic blasts (VLBs).

Comparison of Acute Myeloid Leukemia Measurable Residual Disease Detection By Flow Cytometry in Peripheral Blood and Bone Marrow
Colin Godwin, MD
Poster
Session 617
Hall B, Level 2 (Orange County Convention Center)

The current recommendation against the need for bone marrow aspiration (BMA) in routine follow-of persons with acute myeloid leukemia (AML) in remission preceded the recognition that multiparameter flow cytometry (MFC) is a sensitive and specific means to detect imminent morphologic relapse. Given this recognition, we wondered whether BMA is now necessary, or if concordance between MFC results in peripheral blood (PB) and BMA is such as to make BMA unnecessary, at least for evaluation of measurable residual disease (MRD) by MFC. Previous studies have demonstrated a strong correlation between disease detection by MFC in PB and BMA. Here we examined 724 paired PB and BMA samples from 482 patients to further examine the concordance between PB and BMA blast detection by MFC, particularly among patients in morphologic remission.

Results of the Phase 3 VITAL Study of NEOD001 (Birtamimab) Plus Standard of Care in Patients with Light Chain (AL) Amyloidosis Suggest Survival Benefit for Mayo Stage IV Patients
Edward N. Libby, MD
Poster
Session 653
Orange County Convention Center, Hall B

AL amyloidosis is a rare, progressive, and typically fatal disease caused by both soluble and insoluble (amyloid) forms of misfolded immunoglobulin light chain (LC) proteins, with no approved treatments. Production and tissue deposition of LC aggregates result in various organ system dysfunction (most commonly cardiac and renal), causing significant morbidity and mortality. NEOD001 is an investigational humanized IGg1 designed to directly neutralize soluble toxic aggregates of misfolded LCs and promote phagocytic clearance of amyloid deposits.

The Long Road to Develop Adoptive Therapy with T cells that can Effectively Target AML and Other Malignancies
Philip Greenberg, MD
Hall D, Level 2 (Orange County Convention Center)

E. Donnall Thomas Lecture and Prize

Post-Transplant Work Status of Young Adult Survivors of Allogeneic Hematopoietic Cell Transplant: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR)
Neel S. Bhatt
Oral
Session 706
Orange County Convention Center, Valencia D (W415D)

Return to full-time work after hematopoietic cell transplant (HCT) is an important indicator of health recovery and overall function of survivors. Because young adult (YA) HCT patients are at a critical personal and professional developmental phase at the time of their illness, they face unique challenges potentially impacting their ability to work post-HCT. We aimed to assess the post-HCT work status of YA patients undergoing allogeneic HCT and examine pre-HCT factors associated with their work status at the 1-year time-point post-HCT.

Gene Expression Signature Predicts Deep Molecular Response (DMR) in Chronic Myeloid Leukemia (CML): An Exploratory Biomarker Analysis from ENESTnd
Jerald P. Radich, MD
Oral
Session 632
W308, Level 3 (Orange County Convention Center)

Achieving sustained DMR (variably described as ≥ MR4 or ≥ MR4.5) is an emerging treatment goal for patients with CML. DMR is associated with excellent long-term clinical outcomes and a higher likelihood of successful treatment-free remission (TFR) upon discontinuation of tyrosine kinase inhibitor (TKI) therapy. Biological predictors of patients likely to achieve DMR are unknown. Here, we present an exploratory analysis of gene expression signatures in order to predict DMR to TKI therapy, as well as understand the biological underpinnings that allow a DMR, based on patients treated with imatinib or nilotinib in the ENESTnd study (NCT00471497).

Clonal Hematopoiesis in Donor-Recipient Pairs After Allogeneic Hematopoietic Cell Transplantation
Masumi Ueda, MD
Oral
Session 723
W304EFGH, Level 3 (Orange County Convention Center)

After allogeneic hematopoietic cell transplantation (HCT), a relatively small number of donor hematopoietic cells must reconstitute the entire recipient hematopoietic system, while the donor is left with a near normal pool of hematopoietic cells. We hypothesized that the increased replicative demand on donor cells in the recipient after allogeneic HCT will accelerate telomere shortening and magnify the genetic alterations that are associated with normal aging, including clonal hematopoiesis. We aimed to compare mutation frequency in genes associated with clonal hematopoiesis of indeterminant potential (CHIP) and myeloid diseases between donors and recipients, with a focus on transplant pairs with older donors.

Outcomes Research—Malignant Conditions (Lymphoid Disease): CAR T and Novel Therapies Coming of Age: Real-World and Patient-Centered Outcomes
Chaitra S. Ujjani, MD
Oral
Session 905
Orange County Convention Center, Valencia A (W415A)

Hematology Disease Topics & Pathways

Management of Sickle Cell Disease Complications Beyond Acute Chest
Oyebimpe O. Adesina, MD, MS
Oral
Tangerine 1 (WF1), Level 2 (Orange County Convention Center)

Education Program

Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Mechanisms of and Therapies for cGVHD
Paul J Martin, MD
Oral
Session 722
W230, Level 2 (Orange County Convention Center)

Hematology Disease Topics & Pathways

High Incidence of Herpes Zoster after Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis
Elisabetta Xue, PhD
Poster
Session 723
Hall B, Level 2 (Orange County Convention Center)

Herpes zoster (HZ) after hematopoietic cell transplant (HCT) is a well-known complication with a peak incidence during the first year post-HCT. Cord blood transplant (CBT) recipients are at increased risk for viral infections and historically have a cumulative incidence of HZ approaching 80% by 2.5 years in the context of short-term peri-HCT antiviral prophylaxis. In 2009, international guidelines for prevention of infections after HCT recommended maintaining HZ prophylaxis for at least 1 year after HCT. We retrospectively studied the impact of longer-term antiviral prophylaxis on the incidence of HZ after CBT.

D-Dimer As a Prognostic Biomarker for Venous Thromboembolism after Hematopoietic Cell Transplantation
Ang Li, MD
Poster
Session 331
Hall B, Level 2 (Orange County Convention Center)

 

D-dimer has been well characterized as a prognostic biomarker for venous thromboembolism (VTE) in both the general population and cancer patients. However, it is unclear if D-dimer has prognostic value after hematopoietic transplantation (HCT) in the context of regimen-related toxicity, immune dysregulation, and infectious complications. In the current study, we examined the utility of biomarkers of coagulation activation and fibrinolysis (D-dimer, PAI-1, and TPA) as prognostic and diagnostic biomarkers for VTE post-transplant.

Comparative Effectiveness of Rasburicase Versus Allopurinol for Cancer Patients with Renal Dysfunction and Hyperuricemia
Kylee L. Martens, MD
Poster
Session 901
Hall B, Level 2 (Orange County Convention Center)

While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes in tumor lysis syndrome (TLS) is unknown. There are no studies demonstrating improvement of acute kidney injury (AKI) in patients with TLS and pre-existing renal dysfunction. In this study, we aim to address the comparative effectiveness of rasburicase versus allopurinol in cancer patients with hyperuricemia and AKI.

Rapid and Durable Responses with the SYK/JAK Inhibitor Cerdulatinib in a Phase 2 Study in Relapsed/Refractory Follicular Lymphoma—Alone or in Combination with Rituximab
Stephen Douglas Smith, MD
Poster
Session 623
Hall B, Level 2 (Orange County Convention Center)

Despite recent advances, follicular lymphoma (FL) remains incurable for most patients. Relapsed/refractory (r/r) FL is associated with decremental treatment responses, accumulating toxicity, and poor survival among early failures of 1st line chemoimmunotherapy. Underscored by the recent approvals of idelalisib, copanlisib, and duvelisib, targeting B-cell receptor (BCR) signaling produces ORR of ~50% in r/r patients; however, new agents with a better therapeutic index over long-term administration are needed.

High Rate of Exclusion of HIV Infected Patients from Modern Lymphoma Studies: An Analysis of Current United States Therapeutic Trials
Manoj P. Menon, MD
Poster
Session 902
Hall B, Level 2 (Orange County Convention Center)

Patients infected with HIV have an 8 to 150-fold risk of lymphoma compared to HIV uninfected patients, with certain aggressive non-Hodgkin lymphoma (NHL) histologies being AIDS-defining. Despite the decrease in incidence of both NHL and Hodgkin lymphoma (HL) in the current anti-retroviral treatment (ART) era, HIV-infected patients remain at significantly increased risk of lymphoma compared to the general population.

Over the last decade, advances have been made in the treatment of both NHL and HL with 18 agents approved since 2009. Unfortunately, safety and efficacy data in the HIV-infected population have been lacking in part due to exclusion of such patients from clinical trials. As such, the optimal treatment of HIV-associated lymphomas is unknown. In 2017, the National Comprehensive Care Network (NCCN) and the American Society of Clinical Oncology (ASCO) advocated expanding clinical trial opportunities for HIV-infected patients. However, exclusion criteria precluding HIV-infected patient participation likely persist. We sought to document and describe the current status of clinical trial exclusion criteria for NHL and HL as they relate to HIV infection.

Mapping the Road of Gvhd and GVT: A Longitudinal Study of Immune-Transcriptome Signatures As Novel Approach to Solve Post-Allogeneic Hematopoietic Cell Transplantation Dilemmas
Merav Bar, MD
Poster
Session 722
Hall B, Level 2 (Orange County Convention Center)

Allogeneic Hematopoietic Cell Transplantation (allo HCT) is currently the only curative therapy for high-risk hematologic malignancies due to the immune response of the donor cells against the malignant cells (graft versus tumor effect; GVT), but with the cost of Graft Versus Host Disease (GVHD). Despite extensive research, very few predictors of GVHD and GVT have been identified to date. Additionally, clinical GVHD diagnosis can be challenging due to chemotherapy-related or infection-related organ toxicity manifestations, which further complicate prediction and treatment stratification algorithms.

In order to study the mechanisms of GVHD and GVT and to identify potential GVHD markers we apply a novel approach, called Transcriptome Fingerprint Assay (TFA), relying on high frequency sampling and blood transcript profiling. The TFA is a multiplex microfluidics q-PCR based assay linked with a computational model for modular functional transcriptome analyses, uniquely tailored to answer complex questions on immune perturbations through frequent profiling of gene expression signatures from < 1 ml of blood (Chaussabel and Baldwin. Nat Rev Immunol 2014, Speake et al. Clin Exp Immunol 2017). This approach has been successfully applied to stratify patients’ prognosis in autoimmune and infectious diseases (Banchereau R et al. Cell 2016, Dunning et al. Nat Immunol 2018). In our study we use the TFA to capture longitudinal immune signatures as dynamic “snapshots” of the patient’s immune system after HCT.

Comparison of Outcomes between HSCT Donor Sources for Pediatric Patients with Hematologic Malignancies
Lauren O. Longo
Poster
Session 732
Hall B, Level 2 (Orange County Convention Center)

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for pediatric patients with hematologic malignancies. Historically, matched sibling donors (MSD) have been the preferred donor source given ease of availability and lower rates of graft-versus-host-disease (GVHD). However, only 30% of patients have a MSD and relapse rates are high after MSD HSCT, raising the question of best donor choice. As conditioning regimens evolve, GVHD management improves and supportive care advances, it is important to evaluate the role of donor source on short and long-term clinical outcomes to inform donor selection. We performed a single-center retrospective analysis comparing post-HSCT outcomes in a cohort of pediatric patients undergoing MSD, matched unrelated donor (MUD), and umbilical cord blood (CB) transplants from 2006 to 2018.

Impact of Depth of Pretransplant Clinical Response on Outcomes of Acute Myeloid Leukemia Patients in First Complete Remission (AML-CR1) Who Undergo Allogeneic Hematopoietic Cell Transplantation (AlloHCT)
Mary-Beth M. Percival, MD
Poster
Session 732
Hall B, Level 2 (Orange County Convention Center)

AML patients with intermediate or high-risk features often undergo allogeneic hematopoietic cell transplantation (alloHCT) during first complete remission (CR). The 2017 European LeukemiaNet guidelines for AML specify categories of CR: both with and without count recovery (CR vs. CRi) and with and without measurable residual disease (MRD). Previous smaller retrospective studies have suggested poorer survival outcomes after alloHCT for patients with responses less than CR.

Phase 1 Trial of Cladribine, High-Dose Cytarabine, GCSF, and Dose-Escalated Mitoxantrone (CLAG-M) Plus Gemtuzumab Ozogamicin in Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid Neoplasm
Colin Godwin, MD
Poster
Session 615
Hall B, Level 2 (Orange County Convention Center)

We recently found that CLAG-M was safe and produced higher rates of CR/CRi and higher measurable residual disease (MRD)-negative CR (measured by multiparameter flow cytometry [MFC]) than standard “7+3” therapy in fit patients with newly-diagnosed AML or other high-grade myeloid neoplasm with ≥10% blasts (HG-MN). Since addition of the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO) to chemotherapy reduces relapse risk and improves survival in some AML patients, we conducted a phase 1 study (NCT03531918) to determine the maximum tolerated dose (MTD) of GO with CLAG-M in fit adults with newly-diagnosed AML (APL excluded) or HG-MN.

Frequency, and Effect on Survival, of Ineligibility for Clinical Trials in Newly Diagnosed Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Mary-Beth M. Percival, MD
Poster
Session 613
Hall B, Level 2 (Orange County Convention Center)

Although National Comprehensive Cancer Network guidelines state “the best management of any patient with cancer is in a clinical trial,” few adults with cancer participate in clinical trials. Consequently, ASCO and similar organizations have suggested modifications to eligibility criteria with the goal of increasing participation in clinical trials without a major increase in toxicity. Here we examine the effect of standard exclusion criteria on the ability to enroll patients with newly-diagnosed acute myeloid leukemia (AML) or high-grade myeloid neoplasms (≥10% blasts) on clinical trials. We compare survival outcomes of patients according to eligibility defined based on standard exclusion criteria.

Relapsed or Refractory CLL after CD19-specific CAR-T Therapy: Treatment Patterns and Clinical Outcomes
Mazyar Shadman, MD, MPH
Poster
Session 642
Hall B, Level 2 (Orange County Convention Center)

Treatment of high-risk CLL remains challenging despite the introduction of novel therapeutic agents. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising efficacy in these patients (pts) (Turtle, JCO, 2017; Gauthier, ASH, 2019), but progressive disease after CAR-T is not uncommon. Understanding the outcomes of pts with relapsed or refractory CLL after CAR-T is important for establishing a benchmark for trials in this setting and to study optimal treatment sequencing in high-risk CLL.

Reduced Antigen Presentation May Contribute to Immunomodulatory Drug Resistance in Multiple Myeloma
David G. Coffey, MD
Poster
Session 651
Hall B, Level 2 (Orange County Convention Center)

Maintenance therapy with the immunomodulatory drug (IMiD) lenalidomide improves progression-free survival (PFS) and overall survival among patients with multiple myeloma (MM). It has been suggested that IMiDs enhance immune-mediated anti-tumor responses through increased activation and proliferation of T cells and natural killer (NK) cells as well as inhibition of regulatory T cells. Despite the effectiveness of this therapy, nearly all patients relapse for reasons that remain uncharacterized. We sought to elucidate mechanisms of resistance to lenalidomide maintenance through investigation of mutations in cell-free DNA (cfDNA) and identification of changes in the innate and adaptive immune system by single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs). While MM is a cancer of plasma cells that primarily reside in the bone marrow, we focused on the peripheral blood which offers a comprehensive view of multiple sites of disease including extramedullary locations commonly found at the time of relapse.

A Phase II, Multicenter Study of High Dose Chemotherapy with Autologous Stem Cell Transplant Followed By Maintenance Therapy with Romidepsin for T-Cell Lymphoma
Andrei R. Shustov, MD
Poster
Session 624
Hall B, Level 2 (Orange County Convention Center)

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of aggressive non-Hodgkin lymphomas, with suboptimal outcomes with conventional chemotherapy. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first remission. However, progression-free survival (PFS) after AHCT is only 36-45% (d’Amore et al JCO 2012, Reimer et al JCO 2009), signifying an unmet therapeutic need for improving outcomes post-transplant. Maintenance therapy after AHCT may improve PFS. Romidepsin is a histone deacetylase (HDAC) inhibitor that is FDA approved for the treatment of relapsed/refractory T-cell lymphoma, and is a potential option for maintenance therapy. We present the results of the first multicenter study to evaluate the PFS of patients receiving maintenance therapy after upfront AHCT in PTCL patients.

CRISPR/Cas9-Mediated Protection of Normal Hematopoiesis Combined with the CD33/CD3 Bispecific T-Cell Engager (BiTE) Antibody AMG330 for Improved AML Therapy
Olivier M. Humbert, PhD
Poster
Session 701
Hall B, Level 2 (Orange County Convention Center)

While survival for patients with acute myeloid leukemia (AML) has increased in recent years, relapse and treatment-related mortality remain a significant problem, especially in older patients. Although the use of gemtuzumab ozogamicin (GO) has validated the concept of antibody directed therapy for AML targeting CD33, complications from myelosuppression and opportunistic infections due to on-target toxicity to normal CD33+ hematopoietic cells have limited this approach. In addition, only a subset of patients derives long-term benefit from GO. Thus, to improve the outcomes of CD33-targeted immunotherapy, more potent drugs are needed such as CD33/CD3 bispecific T-cell Engagers (BiTEs), as are strategies to protect normal blood cells from the cytotoxic effects of these agents.

Patient-Reported Neuropsychiatric Outcomes of Long-Term Survivors after Chimeric Antigen Receptor (CAR)-T Cell Therapy
Merav Bar, MD
Poster
Session 704
Hall B, Level 2 (Orange County Convention Center)

CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is a novel treatment with promising results for patients with relapsed/refractory lymphoid malignancies. CAR-T cell therapy has known early toxicities of cytokine release syndrome (CRS) and neurotoxicity, but little is known about long-term neuropsychiatric adverse effects.

We have utilized patient-reported outcomes (PROs), including PROMIS®measures, to assess outcomes of patients with relapse/refractory chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL) who were treated with CD19-targeted CAR-T cells on a clinical trial in our institution (NCT01865617) and survived at least one year after treatment.

Meta-Analysis and Cost-Effectiveness Analysis of Low-Dose Direct Oral Anticoagulant for the Prevention of Cancer Associated Thrombosis
Ang Li, MD
Poster
Session 901
Hall B, Level 2 (Orange County Convention Center)

Randomized controlled trials (RCTs) have shown similar yet conflicting primary outcomes for the use of low-dose direct oral anticoagulant (DOAC), including rivaroxaban and apixaban, in the prevention of cancer-associated thrombosis (CAT). It remains unclear if this preventive strategy is consistent, robust, and cost-effective across different trial populations.

Integrated Single Cell Transcriptomics Defines an Engineered Niche Supporting Hematopoietic Stem Cell Development Ex Vivo
Brandon K. Hadland, MD, PhD
Poster
Session 501
Hall B, Level 2 (Orange County Convention Center)

During embryonic development, hematopoietic stem cells (HSC) arise from hemogenic endothelial cells (HEC) within arterial vessels such as the aorta of the AGM (aorta-gonad-mesonephros) region, in a process referred to as the endothelial to hematopoietic transition (EHT). Although numerous signal pathways have been implicated in EHT, the precise combination of niche-derived signals required to support the generation and self-renewal of functional, long-term engrafting HSC remains poorly defined. To elucidate the niche signals regulating HSC emergence, we used single cell RNA-sequencing to simultaneously analyze the global transcriptional profiles of HEC during their transition to HSC and the AGM-derived endothelial cell stroma (AGM-EC) that supports the generation and expansion of functional HSC. Trajectory analysis of single cell transcriptomes enabled reconstruction of EHT in pseudotime, revealing dynamics of gene expression, including genes encoding cell surface receptors and downstream pathways, during the process of HSC genesis and self-renewal in vivo and in vitro. Transcriptional profiles of niche AGM-EC enabled identification of corresponding ligands which serve to activate these receptors during HSC generation. We integrated this knowledge to engineer a stromal cell-free niche for generation of engrafting HSC from hemogenic precursors in vitro. Specifically, we defined serum-free conditions combining immobilized Notch1 and Notch2-specific antibodies to activate Notch receptors, recombinant VCAM1-Fc chimera or fibronectin fragment to bind VLA-4 integrin, recombinant interleukin-3, stem cell factor, thrombopoietin, and CXCL12 to activate their respective cytokine/chemokine receptors, and small molecule inhibition of TGF-β Receptor

Clinical Experience of CAR T Cell Immunotherapy for Relapsed and Refractory Infant ALL Demonstrates Feasibility and Favorable Responses
Colleen E. Annesley, MD
Poster
Session 614
Hall B, Level 2 (Orange County Convention Center)

The youngest patients referred for CAR T cell therapy are those with relapsed or refractory (R/R) KMT2A-rearranged infant B-ALL. Infants with relapsed ALL following Interfant-99 therapy have a dismal reported 3-yr OS of 20.9%, indicating the need for novel therapies. Smaller patient size, heavily pre-treated disease and high leukemia burden are often characteristics of this subgroup of patients that pose unique challenges to apheresis and manufacture of a T cell product. Additionally, reports of KMT2A-rearranged leukemia undergoing lineage switch following CD19-targeting pressure raises concern for an increased risk of myeloid leukemia relapses after B-lineage targeted CAR T cell therapy in this population. Here we report our experience using CAR T cell immunotherapy for patients with R/R infant ALL enrolled on clinical trials PLAT-02 (NCT02028455) and PLAT-05 (NCT03330691).

Speakers
More than 50 members of our leading-edge research team will be sharing their latest findings. Here are some of the highlights.
David G. Maloney, MD, PhD
  • Medical Director, Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance 
  • Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
  • Professor of Medicine, Division of Oncology, University of Washington

Chronic lymphocytic leukemia, lymphoma, Waldenström macroglobulinemia

Hit the Ground Running: What You Need to Know About CAR T-Cell Therapy
Hit the Ground Running: What You Need to Know About CAR T-Cell Therapy : Friday Satellite Symposia
Regency T-V (Hyatt Regency Orlando)

This live symposium will prepare the hematologists/oncologists in attendance with the knowledge needed to understand and analyze all of the data on CAR T-cell therapy that will be presented during the 2019 ASH annual meeting. Experts on CAR T-cell therapy will discuss the basics of this therapy, clinical trial data for approved and emerging CAR T-cell products, and best practices for managing therapy-related adverse events. During the symposium, faculty will highlight must-see upcoming ASH presentations and posters, highlights of new key data and review of pivotal trials, and practical information about how to identify eligible patients and when to refer to a specialty center.

Chaitra S. Ujjani, MD
  • Medical Oncologist, Seattle Cancer Care Alliance
  • Clinical Associate Professor, Division of Medical Oncology, University of Washington School of Medicine

Hematology oncology

Veneto-STOP Study: Sequential Assessment of Minimal Residual Disease By Next Generation Sequencing to Optimize Outcomes and Minimize Exposure in Venetoclax-Treated CLL Patients
Veneto-STOP Study: Sequential Assessment of Minimal Residual Disease By Next Generation Sequencing to Optimize Outcomes and Minimize Exposure in Venetoclax-Treated CLL Patients : Session 642
Poster
Hall B, Level 2 (Orange County Convention Center)

The treatment indications for venetoclax in CLL are broadening quickly. While the initial approval was for relapsed patients with del 17p (Stilgenbauer S, et al. JCO 2018), it has subsequently been extended to all patients (Seymour J, et al. NEJM 2018, Fischer K, et al. NEJM 2019). The duration of therapy with each approval has evolved as well, from continuing therapy until progression/toxicity to 1 year in front-line CLL. The limited durations of therapy were applied to all patients based on trial design and were not dependent on response to treatment.

Undetectable minimal residual disease (U-MRD) with venetoclax is associated with improved progression-free survival (PFS), both as a single agent and in combination with rituximab (Stilgenbauer S, et al. JCO 2018, Seymour J, et al. NEJM 2018). Early phase data suggest that patients who discontinue venetoclax after achieving MRD negativity can be monitored off therapy and successfully retreated upon relapse (Seymour J, et al, Lancet Onc 2017). However, patients who discontinue therapy with persistent residual disease have a higher incidence of relapse (Kater A, et al. JCO 2019).

Together, these data suggest that the duration of venetoclax therapy should be individualized, based on the depth of response one achieves and not a fixed duration schedule. Therefore, we propose a prospective clinical trial, utilizing MRD assessment with a next generation sequencing (clonoSEQ®) assay to guide clinical decision making in patients with CLL receiving venetoclax-based regimens.

Outcomes Research—Malignant Conditions (Lymphoid Disease): CAR T and Novel Therapies Coming of Age: Real-World and Patient-Centered Outcomes
Outcomes Research—Malignant Conditions (Lymphoid Disease): CAR T and Novel Therapies Coming of Age: Real-World and Patient-Centered Outcomes : Session 905
Oral
Orange County Convention Center, Valencia A (W415A)

Hematology Disease Topics & Pathways

Neel S. Bhatt, MBBS, MPH

Assistant Professor, Department of Pediatrics
University of Washington School of Medicine
Assistant Member, Clinical Research Division
Fred Hutchinson Cancer Research Center
 

Post-Transplant Work Status of Young Adult Survivors of Allogeneic Hematopoietic Cell Transplant: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR)
Post-Transplant Work Status of Young Adult Survivors of Allogeneic Hematopoietic Cell Transplant: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR) : Session 706
Oral
Orange County Convention Center, Valencia D (W415D)

Return to full-time work after hematopoietic cell transplant (HCT) is an important indicator of health recovery and overall function of survivors. Because young adult (YA) HCT patients are at a critical personal and professional developmental phase at the time of their illness, they face unique challenges potentially impacting their ability to work post-HCT. We aimed to assess the post-HCT work status of YA patients undergoing allogeneic HCT and examine pre-HCT factors associated with their work status at the 1-year time-point post-HCT.

Andrew J. Cowan, MD
  • Hematologist Oncologist, Seattle Cancer Care Alliance
  • Assistant Professor, University of Washington

Multiple myeloma, amyloidosis, Waldenström macroglobulinemia, monoclonal gammopathy, smoldering myeloma, plasmacytoma, POEMS syndrome, plasma cell leukemia and Castleman disease. 

The Global State of Hematopoietic Stem Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation (WBMT) Database and the Global Burden of Disease Study
The Global State of Hematopoietic Stem Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation (WBMT) Database and the Global Burden of Disease Study : Session 902
Oral
Orange County Convention Center, W307

Multiple myeloma (MM), is a clonal plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. MM is a global disease – worldwide in 2016, there were 138509 incident cases with an age standardized incidence rate (ASIR) of 2.1 per 100 000 persons, with a 126% global increase in incident cases from 1990 to 2016 (Cowan AJ et al JAMA Oncology 2018). Access to effective care, including proteasome inhibitors, immunomodulatory agents, and autologous hematopoietic stem cell transplantation (HSCT) is largely limited to high-income sociodemographic index (SDI) countries. SCT remains the standard of care for eligible patients, and in general is more affordable and accessible worldwide than novel therapies. We sought to evaluate the rates and utilization of ASCT globally from 2006-2015 to better characterize access to SCT for patients with MM.

Efficacy and Safety of Fully Human Bcma CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase Bcma Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma
Efficacy and Safety of Fully Human Bcma CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase Bcma Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma : Session 704
Oral
Valencia A (W415A), Level 4 (Orange County Convention Center)

Although the median survival for patients with multiple myeloma has improved dramatically, almost all patients will eventually relapse and become resistant to standard therapies. Chimeric antigen receptor T cells (CAR T cells) targeting B cell maturation antigen (BCMA) have shown early promise in MM, with high initial response rates. Responses are often incomplete and durability has been a key concern, with most patients relapsing within 1 year (Raje N et al NEJM 2019). We have previously demonstrated that gamma secretase inhibitors (GSI) increase BCMA surface density, decrease soluble BCMA levels and augment anti-tumor efficacy of BCMA CAR T cells in preclinical models. In a phase I first-in-human trial (NCT03502577), we combined CAR T cells expressing a fully human BCMA scFv with an orally administered gamma secretase inhibitor (JSMD194).

Ajay K. Gopal, MD
  • Professor, Medical Oncology Division, University of Washington School of Medicine
  • Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
  • Director of Clinical Research, Hematology Malignancies/Hematology, Seattle Cancer Care Alliance

Diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, low grade lymphoma, Waldenström macroglobulinemia, MALT, mantle cell lymphoma and marginal zone lymphoma. 

Indolent Lymphomas: The Marathon Has a New Course
Indolent Lymphomas: The Marathon Has a New Course
OCCC, Tangerine 1 (WF1)

The treatment of indolent B cell non-Hodgkin lymphoma has evolved beyond the sequencing of multiple lines of combination chemotherapy. This session will focus on new strategies for these diseases, including new ways to target CD20, existing and new targeted therapies and combinations, and new immunotherapeutic approaches and tumor antigens. Lastly, we will review where autologous and allogeneic stem cell transplantation fit amidst these increasing treatment options.

Indolent Lymphomas: The Marathon Has a New Course
Indolent Lymphomas: The Marathon Has a New Course
Tangerine 1 (WF1), Level 2 (Orange County Convention Center)

The treatment of indolent B cell non-Hodgkin lymphoma has evolved beyond the sequencing of multiple lines of combination chemotherapy. This session will focus on new strategies for these diseases, including new ways to target CD20, existing and new targeted therapies and combinations, and new immunotherapeutic approaches and tumor antigens. Lastly, we will review where autologous and allogeneic stem cell transplantation fit amidst these increasing treatment options.

Indolent Lymphomas: The Marathon Has a New Course
Indolent Lymphomas: The Marathon Has a New Course
Oral
Tangerine 1 (WF1), Level 2 (Orange County Convention Center)

The treatment of indolent B cell non-Hodgkin lymphoma has evolved beyond the sequencing of multiple lines of combination chemotherapy. This session will focus on new strategies for these diseases, including new ways to target CD20, existing and new targeted therapies and combinations, and new immunotherapeutic approaches and tumor antigens. Lastly, we will review where autologous and allogeneic stem cell transplantation fit amidst these increasing treatment options.

Damian J. Green, MD
  • Hematologist Oncologist, Seattle Cancer Care Alliance
  • Associate Member, Fred Hutchinson Cancer Research Center
  • Associate Professor, Medical Oncology, University of Washington School of Medicine 

Multiple myeloma, Waldenström macroglobulinemia, smoldering myeloma, plasmacytoma, plasma cell leukemia, bone marrow transplantation and radioimmunotherapy.

The Role of Antibody Binding Capacity in Bcma CAR-T Cell Therapy for Multiple Myeloma
The Role of Antibody Binding Capacity in Bcma CAR-T Cell Therapy for Multiple Myeloma : Friday Scientific Workshops
W240BCD (Orange County Convention Center)

Chimeric Antigen Receptor T Cell Therapy for PCD With an Emphasis on Multiple Myeloma

Ang Li, MD
  • Physician, Seattle Cancer Care Alliance
  • Acting Instructor, University of Washington School of Medicine

Hematology-oncology, internal medicine

D-Dimer As a Prognostic Biomarker for Venous Thromboembolism after Hematopoietic Cell Transplantation
D-Dimer As a Prognostic Biomarker for Venous Thromboembolism after Hematopoietic Cell Transplantation : Session 331
Poster
Hall B, Level 2 (Orange County Convention Center)

 

D-dimer has been well characterized as a prognostic biomarker for venous thromboembolism (VTE) in both the general population and cancer patients. However, it is unclear if D-dimer has prognostic value after hematopoietic transplantation (HCT) in the context of regimen-related toxicity, immune dysregulation, and infectious complications. In the current study, we examined the utility of biomarkers of coagulation activation and fibrinolysis (D-dimer, PAI-1, and TPA) as prognostic and diagnostic biomarkers for VTE post-transplant.

Meta-Analysis and Cost-Effectiveness Analysis of Low-Dose Direct Oral Anticoagulant for the Prevention of Cancer Associated Thrombosis
Meta-Analysis and Cost-Effectiveness Analysis of Low-Dose Direct Oral Anticoagulant for the Prevention of Cancer Associated Thrombosis : Session 901
Poster
Hall B, Level 2 (Orange County Convention Center)

Randomized controlled trials (RCTs) have shown similar yet conflicting primary outcomes for the use of low-dose direct oral anticoagulant (DOAC), including rivaroxaban and apixaban, in the prevention of cancer-associated thrombosis (CAT). It remains unclear if this preventive strategy is consistent, robust, and cost-effective across different trial populations.

Patterns and Predictors of Emicizumab Adherence in People with Hemophilia
Patterns and Predictors of Emicizumab Adherence in People with Hemophilia : Session 904
Poster
Hall B, Level 2 (Orange County Convention Center)

Emicizumab is a subcutaneously administered, humanized bispecific monoclonal antibody that is recently approved for hemostatic prophylaxis in people with hemophilia A (PWH) with or without factor VIII inhibitors. We hypothesize that the new route and frequency of administration would lead to better treatment adherence compared to factor or bypass products in PWH outside of clinical trials. We performed the current study to test the hypothesis and to examine potential predictors of non-adherence associated with emicizumab treatment.

Soluble C5b-9 As a Prognostic Biomarker for Thrombotic Microangiopathy at the Onset of Graft-Versus-Host Disease
Soluble C5b-9 As a Prognostic Biomarker for Thrombotic Microangiopathy at the Onset of Graft-Versus-Host Disease : Session 721
Oral
Valencia BC (W415BC), Level 4 (Orange County Convention Center)

Thrombotic microangiopathy (TMA) is a known complication of allogeneic hematopoietic cell transplantation (HCT). Though the presence of graft-versus-host disease (GVHD) predicts the development of TMA, only a small subset of patients with GVHD will develop this condition. In the current study, we examined soluble C5b-9 (sC5b9), the terminal complement complex, as a potential biomarker for the development of TMA among patients with active GVHD.

Ryan C. Lynch, MD
  • Assistant Professor, UW School of Medicine
  • Assistant Member, Fred Hutchinson Cancer Research Center

Chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, mantle cell lymphoma and marginal zone lymphoma.

Low Achievement of End of Life Quality Measures in Large B-Cell Lymphoma Patients Who Progressed after CD19-Specific CAR-T Cell Therapy
Low Achievement of End of Life Quality Measures in Large B-Cell Lymphoma Patients Who Progressed after CD19-Specific CAR-T Cell Therapy : Session 902
Oral
W307, Level 3 (Orange County Convention Center)

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is FDA-approved in patients with relapsed or refractory large B-cell lymphomas and can lead to long-term remissions in 35-40% of patients. Outcomes in patients who progress after CAR T-cell therapy is poor, with a median overall survival (OS) of 5.3 months with few long-term survivors (Chow et al. AJH 2019). Achieving quality end of life (EOL) care for patients with hematologic malignancies has been a challenge, and widespread consensus on what are acceptable metrics is lacking (Odejide et al JCO 2016). EOL care among large B-cell lymphoma patients who progressed after CAR-T cell therapy has not been previously examined.

Impact of Lab Abnormalities at the Time of Progression in Patients Receiving CD19-Specific CAR T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphomas
Impact of Lab Abnormalities at the Time of Progression in Patients Receiving CD19-Specific CAR T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphomas : Session 627
Poster
Hall B, Level 2 (Orange County Convention Center)

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is FDA approved in patients with relapsed or refractory large B-cell lymphomas. While 35-40% of patients may achieve a durable complete response (CR), the toxicity incurred with CAR-T therapy could impact the ability to receive subsequent treatment in those who progress after CAR-T infusion. Our prior data suggested that patients who experienced early progression had inferior overall survival. We now update our results and evaluate the impact of laboratory abnormalities and comorbidities at the time of progression on overall survival.

Filippo Milano, MD, PhD
  • Assistant Professor, UW School of Medicine
  • Assistant Member, Fred Hutchinson Cancer Research Center
  • Associate Director, Cord Blood Transplant Program, Fred Hutchinson Cancer Research Center

Cord blood transplantation, acute leukemias

No Engraftment Advantage after Single or Double Umbilical Cord Blood Transplant (CBT) with the Addition of a Non-HLA Matched Off-the-Shelf Expanded Cord Blood Unit Compared to Conventional CBT: Results of a Randomized Trial
No Engraftment Advantage after Single or Double Umbilical Cord Blood Transplant (CBT) with the Addition of a Non-HLA Matched Off-the-Shelf Expanded Cord Blood Unit Compared to Conventional CBT: Results of a Randomized Trial : Session 732
Oral
W307, Level 3 (Orange County Convention Center)

Based on pilot study data demonstrating safety and excellent survival [Blood 2014 124:46] in acute leukemia patients undergoing myeloablative cord blood transplant (CBT) plus infusion of an off-the-shelf non-HLA matched expanded CB unit (OTS) for bridging hematopoiesis, a randomized trial was conducted to determine whether myeloablative CBT with or without an OTS would confer more rapid neutrophil (ANC) engraftment and therefore a survival advantage.

Jerald P. Radich, MD
  • Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
  • Associate Professor, Medical Oncology Division, University of Washington School of Medicine

Molecular genetics of leukemia and the detection of minimal residual disease; CML

Analyses of Predictors of Durable Treatment-Free Remission in Patients with Chronic Myeloid Leukemia in Chronic Phase Following Frontline or Second-Line Nilotinib
Analyses of Predictors of Durable Treatment-Free Remission in Patients with Chronic Myeloid Leukemia in Chronic Phase Following Frontline or Second-Line Nilotinib : Session 632
Poster
Hall B, Level 2 (Orange County Convention Center)

Some patients with chronic myeloid leukemia in chronic phase (CML-CP) who have a sustained deep molecular response (DMR) with tyrosine kinase inhibitors (TKIs) can discontinue therapy and achieve treatment-free remission (TFR). Thus far, no consistent variables that predict TFR have been identified. In long-term follow-up of patients who attempted TFR following front- or second-line nilotinib in the ENESTfreedom and ENESTop TFR studies, respectively, 192-week TFR rates were 44.2% (ENESTfreedom) and 46.0% (ENESTop), and adverse event rates tended to decrease over time during TFR. Previous analyses in ENESTfreedom suggested that lower Sokal risk score and consistent MR4.5 (BCR-ABL1 ≤ 0.0032% on the International Scale [IS]) in the consolidation phase were associated with maintaining TFR, whereas in ENESTop, a longer time in MR4.5 was associated with maintaining TFR. We sought to identify clinical predictors of a durable TFR by analyzing pooled data from ENESTfreedom and ENESTop.

Gene Expression Signature Predicts Deep Molecular Response (DMR) in Chronic Myeloid Leukemia (CML): An Exploratory Biomarker Analysis from ENESTnd
Gene Expression Signature Predicts Deep Molecular Response (DMR) in Chronic Myeloid Leukemia (CML): An Exploratory Biomarker Analysis from ENESTnd : Session 632
Oral
W308, Level 3 (Orange County Convention Center)

Achieving sustained DMR (variably described as ≥ MR4 or ≥ MR4.5) is an emerging treatment goal for patients with CML. DMR is associated with excellent long-term clinical outcomes and a higher likelihood of successful treatment-free remission (TFR) upon discontinuation of tyrosine kinase inhibitor (TKI) therapy. Biological predictors of patients likely to achieve DMR are unknown. Here, we present an exploratory analysis of gene expression signatures in order to predict DMR to TKI therapy, as well as understand the biological underpinnings that allow a DMR, based on patients treated with imatinib or nilotinib in the ENESTnd study (NCT00471497).

Brenda M. Sandmaier, MD
  • Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
  • Professor, Medical Oncology Division, University of Washington School of Medicine

Hematopoietic cell transplantation using HLA-matched & mismatched donors; development of nonmyeloablative conditioning regimens; reduced-intensity conditioning

Sirolimus Combined with Cyclosporine (CSP) and Mycophenolate Mofetil (MMF) As Graft-Vs-Host Disease (GVHD) Prophylaxis after Nonmyeloablative (NMA) Hematopoietic Cell Transplantation (HCT) Using HLA Class I or Class II Antigen Mismatched Donors
Sirolimus Combined with Cyclosporine (CSP) and Mycophenolate Mofetil (MMF) As Graft-Vs-Host Disease (GVHD) Prophylaxis after Nonmyeloablative (NMA) Hematopoietic Cell Transplantation (HCT) Using HLA Class I or Class II Antigen Mismatched Donors : Session 722
Oral
W230, Level 2 (Orange County Convention Center)

The success of HCT is highly dependent on the availability of compatible donors. Depending on ethnicity, fully HLA-matched donors cannot be identified for 25–84% of patients. In an effort to extend the use of HLA-mismatched donors to patients only eligible for NMA HCT, we previously demonstrated that engraftment and long-term survival can be achieved using CSP and MMF immunosuppression after HLA class I antigen-mismatched HCT (Nakamae et al, 2010). Based on this trial, we designed a phase II multi-center trial to assess the efficacy of GVHD prophylaxis with triple immune suppression with CSP, MMF and sirolimus after HLA class I or class II antigen mismatched NMA HCT (fludarabine 90mg/m2 and 2–3 Gy TBI). Patients ineligible for high-dose conditioning with only HLA class I or class II antigen mismatched donors available were eligible for inclusion. The primary objective was to determine whether the incidence of grades 2-4 acute GVHD can be reduced to less than the historical rate of 70% with the triple-immunosuppression. The evaluation was planned to be carried out separately among HLA class I and class II mismatched patients. Secondary objectives included day 100 non-relapse mortality (NRM) and grades 3-4 acute GVHD. CSP was started on day -3 and continued to day +150 and then tapered off by day +180. Sirolimus was started on day -3 through day +180 and then tapered off by day +365. MMF was given thrice daily from days 0 to +30 then twice daily to day +100 and tapered off by day +150. A total of 76 patients were enrolled and received conditioning with fludarabine and TBI followed by infusion of unmodified G-CSF mobilized peripheral blood stem cell (PBSC) grafts. The median age was 63 (21–76) years, and median follow-up of surviving patients was 47 (4–94) months. 51 (67%) and 25 (33%) of patients had HLA class I or II mismatches, respectively. Transplant demographics are summarized in Table 1.

Mazyar Shadman, MD, MPH
  • Assistant Professor, Medical Oncology Division, University of Washington School of Medicine
  • Assistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center

Lymphomas including CLL/SLL and hairy cell leukemia

CD20 Targeted Chimeric Antigen Receptor T-cells (CART) for Treatment of High-Risk B-Cell Non-Hodgkin Lymphomas (B-NHL)
CD20 Targeted Chimeric Antigen Receptor T-cells (CART) for Treatment of High-Risk B-Cell Non-Hodgkin Lymphomas (B-NHL) : Session 704
Poster
Hall B, Level 2

Chimeric antigen receptor T-cells (CAR-T) targeting CD19 have shown clinical efficacy in high-risk B-cell lymphomas, which has led to approval of 2 such therapies (axicabtagene ciloleucel and tisagenlecleucel) for large B-cell lymphoma after 2 lines of treatment. Despite the promising results, complete remission (CR) is achieved in ~ 50% of patients, and with longer follow-up progression-free survival is around 40%. Therefore, finding effective treatments for high-risk B-NHLs remains an unmet need. CD20 is a proven therapeutic target for B-Cell Non-Hodgkin Lymphomas (B-NHL), supported by previously approved naked and radiolabeled anti-CD20 monoclonal antibodies and a number of studies investigating novel bispecific antibodies targeting this antigen. CD20-targeted CAR-T is another potential adoptive immunotherapy option that could be utilized in combination or sequentially before or after CD19 CAR-T, depending on efficacy. Here, we present our ongoing phase I/II clinical trial investigating safety and efficacy of CD20 CAR-T for high-risk B-NHLs (NCT03277729).

Relapsed or Refractory CLL after CD19-specific CAR-T Therapy: Treatment Patterns and Clinical Outcomes
Relapsed or Refractory CLL after CD19-specific CAR-T Therapy: Treatment Patterns and Clinical Outcomes : Session 642
Poster
Hall B, Level 2 (Orange County Convention Center)

Treatment of high-risk CLL remains challenging despite the introduction of novel therapeutic agents. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising efficacy in these patients (pts) (Turtle, JCO, 2017; Gauthier, ASH, 2019), but progressive disease after CAR-T is not uncommon. Understanding the outcomes of pts with relapsed or refractory CLL after CAR-T is important for establishing a benchmark for trials in this setting and to study optimal treatment sequencing in high-risk CLL.

Treatment Discontinuation Patterns for Patients with CLL in the Real-World Settings: Results from a Multi-Center Study
Treatment Discontinuation Patterns for Patients with CLL in the Real-World Settings: Results from a Multi-Center Study : Session 642
Poster
Hall B, Level 2

The recent approval of novel agents (NAs) has changed the treatment landscape in chronic lymphocytic leukemia (CLL), however, there remains uncertainty regarding treatment discontinuation patterns in real-world (RW) settings. This study assessed patterns of and reasons for discontinuation for patients (pts) treated with chemotherapy/chemoimmunotherapy (CT/CIT) and NAs in first (1L) and second (2L) lines of therapy in CLL.

CLL: Therapy, excluding Transplantation: Combination and Novel Treatment
CLL: Therapy, excluding Transplantation: Combination and Novel Treatment : Session 642
Oral
Orange County Convention Center, Hall E1

Moderators: Sameer A. Parikh, MD, Mayo Clinic and Mazyar Shadman, MD, Uw/Fred Hutchinson Cancer Research Center

Masumi Ueda, MD
  • Assistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
  • Assistant Professor, Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine

Bone marrow transplantation, long-term follow-up

Clonal Hematopoiesis in Donor-Recipient Pairs After Allogeneic Hematopoietic Cell Transplantation
Clonal Hematopoiesis in Donor-Recipient Pairs After Allogeneic Hematopoietic Cell Transplantation : Session 723
Oral
W304EFGH, Level 3 (Orange County Convention Center)

After allogeneic hematopoietic cell transplantation (HCT), a relatively small number of donor hematopoietic cells must reconstitute the entire recipient hematopoietic system, while the donor is left with a near normal pool of hematopoietic cells. We hypothesized that the increased replicative demand on donor cells in the recipient after allogeneic HCT will accelerate telomere shortening and magnify the genetic alterations that are associated with normal aging, including clonal hematopoiesis. We aimed to compare mutation frequency in genes associated with clonal hematopoiesis of indeterminant potential (CHIP) and myeloid diseases between donors and recipients, with a focus on transplant pairs with older donors.

Clinical Trials
A Single-Center Phase 1/2 Study of Single- or Fractioned-Dose Gemtuzumab Ozogamicin in Combination with G-CSF, Cladribine, Cytarabine and Mitoxantrone (GCLAM) for Previously Untreated Adult Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm
Roland B. Walter, MD, PhD, MS
NCT03531918

This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte colony stimulating factor (G-CSF), cladribine, cytarabine and mitoxantrone (GCLAM) and to see how well they work in treating participants with acute myeloid leukemia or high-grade myeloid tumors (neoplasms) that have not been previously treated. Antibody-drug conjugates, such as gemtuzumab ozogamicin, act by directly delivering toxic chemotherapy to cancer cells. Granulocyte colony stimulating factor is a growth factor used to stimulate leukemia cells and render them more sensitive to chemotherapy drugs. Drugs used in chemotherapy, such as cladribine, cytarabine and mitoxantrone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gemtuzumab ozogamicin in combination with G-CSF, cladribine, cytarabine and mitoxantrone hydrochloride may work better in treating participants with acute myeloid leukemia or high-grade myeloid neoplasm.
A phase 2 trial of fractionated gemtuzumab ozogamicin to eradicate measurable residual disease in acute myeloid leukemia patients (GO for MRD)
NCT03737955

This phase II trial studies how well fractionated gemtuzumab ozogamicin works in treating measurable residual disease in participants with acute myeloid leukemia. Antibody-drug conjugates, such as gemtuzumab ozogamicin, may block cancer growth in different ways by targeting certain cells.
Addition of Sorafenib to G-CSF, Cladribine, Cytarabine and Mitoxantrone (G-CLAM) in Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD status: A Phase 1/2 Study
Anna B. Halpern, MD
NCT02728050

This phase I/II trial studies the side effects and best dose of filgrastim (granulocyte colony-stimulating factor [G-CSF]), cladribine, cytarabine, and mitoxantrone hydrochloride, when given together with sorafenib tosylate and to see how well they work in treating patients with newly-diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (likely to be more aggressive). Drugs used in chemotherapy, such as filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride together with sorafenib tosylate may kill more cancer cells.
A Randomized Phase II Study to Compare the Net Clinical Benefit of Cyclosporine and Sirolimus combined with MMF or Post-Transplant Cyclophosphamide as GVHD Prophylaxis after HLA-Matched or HLA-Mismatched Unrelated G-CSF Mobilized Blood Cell Transplantation using Nonmyeloablative or Reduced Intensity Conditioning for Patients with Hematologic Malignancies: A Multi-Center Trial
Masumi Ueda, MD
NCT03246906

This randomized phase II trial includes a blood stem cell transplant from an unrelated donor to treat blood cancer. The treatment also includes chemotherapy drugs, but in lower doses than conventional (standard) stem cell transplants. The researchers will compare two different drug combinations used to reduce the risk of a common but serious complication called "graft versus host disease" (GVHD) following the transplant. Two drugs, cyclosporine (CSP) and sirolimus (SIR), will be combined with either mycophenolate mofetil (MMF) or post-transplant cyclophosphamide (PTCy). This part of the transplant procedure is the main research focus of the study.
A Study Evaluating Escalating Doses of 211At-labeled anti-CD45 MAb BC8-B10 (211At-BC8-B10) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)
Brenda M. Sandmaier, MD
NCT03128034

This phase I/II trial studies the side effects and best dose of 211^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.
A Two-Stage Phase 1 Open-Label Study of huJCAR014, CD19-targeted Chimeric Antigen Receptor (CAR)-Modified T cells Bearing a Human Binding Domain, in Adult Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia
Cameron J. Turtle, MBBS, PhD, FRACP, FRCPA
NCT03103971

This phase I trial studies the side effects of autologous human anti-CD19 chimeric antigen receptor (CAR)-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes (huJCAR014) in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces.
A Phase I Study of Adoptive Immunotherapy for Advanced B-cell Maturation Antigen (BCMA)+ Multiple Myeloma with Autologous CD4+ and CD8+ T cells Engineered to Express a BCMA-specific Chimeric Antigen Receptor
Damian J. Green, MD
NCT03338972

This phase I trial studies the side effects and best dose of BCMA CAR-T cells in treating patients with BCMA positive multiple myeloma that has come back or does not respond to treatment. T cells are a type of white blood cell and a major component of the immune system. T-cells that have been genetically modified in the laboratory express BCMA and may kill cancer cells with the protein BCMA on their surface. Giving chemotherapy before BCMA CAR-T cells may reduce the amount of disease and to cause a low lymphocyte (white blood cell) count in the blood, which may help the infused BCMA CAR-T cells survive and expand.
A Phase I Study of B-cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T cells in Combination with JSMD194, a Small Molecule Inhibitor of Gamma Secretase, in Patients with Relapsed or Persistent Multiple Myeloma
Andrew J. Cowan, MD
NCT03502577

This phase I trial determines the side effects and best dose of B-cell maturation antigen (BCMA)-chimeric antigen receptor (CAR) T-cells when combined with gamma-secretase inhibitor LY3039478 (LY3039478), cyclophosphamide, and fludarabine in treating participants with multiple myeloma that that has come back or remains despite treatment. Placing genes added in the laboratory into immune T-cells may make the T-cells recognize BCMA, a protein on the surface of cancer cells. LY3039478 may enhance the killing of cancer cells by increasing the BCMA expression on multiple myeloma cells, making the targeted BCMA CAR-T treatment more effective. LY3039478 also decreases the amount of BCMA found in the circulation (called soluble BCMA) that is not bound to the myeloma cells. LY3039478 can therefore reduce the potential for soluble BCMA to act as a decoy. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BCMA CAR T therapy with LY3039478, cyclophosphamide, and fludarabine may work better in treating participants with relapsed or persistent multiple myeloma.
Phase I Study of Adoptive Immunotherapy with CD8+ and CD4+ Memory T cells Transduced to Express an HA-1-specific T cell Receptor (TCR) for Children and Adults with Recurrent Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT)
Elizabeth F. Krakow, MD, MSc
NCT03326921

This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) T cells in treating patients with acute leukemia that has come back or does not respond to treatment following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.
Phase II Window Study of Pembrolizumab in Untreated B-cell Non-Hodgkin Lymphoproliferative Diseases
Ajay K. Gopal, MD
NCT03498612

This phase II trial studies how well pembrolizumab works in treating participants with B-cell non-Hodgkin lymphoproliferative diseases that have not been treated. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread.
A Pilot Trial of Adriamycin, Pembrolizumab, Vinblastine and Dacarbazine (APVD) for Patients with Untreated Classical Hodgkin Lymphoma
Ryan C. Lynch, MD
NCT03331341

This phase II trial studies the side effects of doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine in treating patients with classical Hodgkin Lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Giving doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine may work better in treating classical Hodgkin lymphoma.
Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM)
Andrew J. Cowan, MD
NCT03937635

This phase III trial studies how well lenalidomide and dexamethasone works with or without daratumumab in treating patients with high-risk smoldering myeloma. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide and dexamethasone with daratumumab may work better in treating patients with smoldering myeloma.
Individualized Treatment for Relapsed/Refractory Multiple Myeloma Based on High Throughput Drug Sensitivity and Genomics Data
Andrew J. Cowan, MD
NCT03389347

This pilot clinical trial studies whether using high throughput drug sensitivity and genomics data is feasible in developing individualized treatment in patients with multiple myeloma or plasma cell leukemia that has come back or does not respond to treatment. High throughput screen tests many different drugs that kill multiple myeloma cells in individual chambers at the same time. Matching a drug or drug combination to a patient using high throughput screen and genetic information may improve the ability to help patients by choosing drugs that work well for their disease.
A Phase II Randomized Controlled Trial Comparing Four GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients with Acute Leukemia: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs. CD34+-Selected Pan T Cell Depletion (CD34+) vs. Post-Transplantation Cyclophosphamide (PTCy) vs. Tacrolimus and Methotrexate (TacMTX) PBSCT.
Marie E. Bleakley, MD, PhD, MMSC
NCT03970096

This phase II trial compares four strategies for the reduction of graft versus host disease in patients with acute leukemia in remission. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patients immune system from rejecting the donors stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient immune cells and help destroy any remaining cancer cells.

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