Enhancing lives with exceptional science. Discover
Seattle Cancer Care Alliance’s groundbreaking research at the most comprehensive hematology event of the year.

On December 1-4, the American Society of Hematology (ASH) will host its 60th 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 2657 through Monday, December 3. 

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.

Outcomes of Patients with Large B-Cell Lymphomas and Progressive Disease Following CD19-Specific CAR T-Cell Therapy
Victor A. Chow, MD
Oral
Session 627
Pacific Ballroom 20, Marriott Marquis San Diego Marina

Background: CD19-specific chimeric antigen receptor (CAR) T-cell therapy has proven to be highly effective in patients with relapsed or refractory large B-cell lymphomas, yielding early complete response (CR) rates of ~40%, which are typically sustained. Unfortunately, most patients will not experience prolonged disease control. Despite this fact, little data exist defining the outcomes and impact of subsequent therapies for such individuals. Limited data also exist on the ability for such patients to pursue further clinical trials or allogeneic hematopoietic stem-cell transplant (HSCT). This project details the specific interventions and outcomes of this population to better inform the management of patients who suffer progressive disease (PD) after CD19-specific CAR T-cell therapy.

The HAS-RISC Score for Venous Thromboembolism (VTE) Risk Stratification in Newly Diagnosed Multiple Myeloma Patients Starting Immunomodulatory Drugs (IMID) 
Ang Li, MD
Oral
Session 331
Room 29C, San Diego Convention Center

Introduction: Patients with newly diagnosed multiple myeloma (MM) have high risk of venous thromboembolism (VTE) when starting initial treatment that contains immunomodulatory drugs (IMID) such as lenalidomide or thalidomide. The National Comprehensive Cancer Network (NCCN) guideline recommends primary anticoagulant thromboprophylaxis for the high-risk patients. However, it is challenging to risk-stratify patients without a validated risk model. We have conducted a retrospective cohort study using the SEER-Medicare (Surveillance, Epidemiology, and End Results) database to derive a new VTE risk assessment model.

Prolonged Lenalidomide Therapy in Multiple Myeloma Patients Does Not Impact Autologous PBSC Mobilization: A Single Center Retrospective Analysis
Andrew J. Cowan, MD
Oral
Session 711
Grand Hall A, Manchester Grand Hyatt San Diego

Background: Autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma (MM). Typically, patients receive several cycles of induction therapy to achieve appropriate cytoreduction prior to ASCT. Since the introduction of lenalidomide into induction therapy, there have been conflicting reports about its impact on subsequent autologous peripheral blood stem cell (PBSC) mobilization. Early reports showed a trend of patients failing PBSC mobilization and collection after lenalidomide when granulocyte colony stimulating factor (GCSF) was employed as a single agent. More recent reports suggested that using chemotherapy in combination with growth factors including plerixafor can overcome failures of mobilization. To address these conflicting reports, we evaluated the impact of prior lenalidomide in a large cohort of MM patients undergoing mobilization and collection at a tertiary stem cell transplant center.

High Throughput Drug Screening of Leukemia Stem Cells Reveals Resistance to Standard Therapies and Sensitivity to Other Agents in Acute Myeloid Leukemia
Pamela S. Becker, MD, PhD
Oral
Session 604
Grand Hall D, Manchester Grand Hyatt San Diego

Background: Leukemia stem cells (LSCs) play a critical role in AML propagation and relapse. Other investigators have also highlighted unique gene expression profiles for the leukemia stem cell population. Here we compared the results of in vitro drug sensitivity testing against a custom panel of drugs and drug combinations for blast populations vs. leukemia stem cell populations derived from the same patients, as well as mutation analysis for a panel of 194 recurrently mutated genes in AML.

Engineering Resistance to CD33-Targeted Immunotherapy in Normal Hematopoiesis By CRISPR/Cas9-Deletion of CD33 Exon 2
Roland B. Walter, MD, PhD, MS
Poster
Session 801
Hall GH, San Diego Convention Center

Background: Improved survival with gemtuzumab ozogamicin (GO) in some people with acute myeloid leukemia has validated CD33 as immunotherapeutic target and sparked interested in developing new, highly potent CD33-directed therapeutics. As a limitation of this treatment strategy, CD33 expression on maturing and mature myeloid cells causes significant on-target, off-leukemia effects. Toxicity of CD33-targeted immunotherapy should be minimal in the presence of normal hematopoietic stem and progenitor cells (HSPCs) engineered to lack CD33 variants recognized by therapeutic antibodies. Indeed, very recent studies have shown that CRISPR/Cas9 with a single guide RNA (gRNA) designed to target the CD33coding region reduces display of CD33 and protects engineered cells from CD33 CAR T-cells. However, this approach resulted in low levels of CD33disruption in vivoand off-target activity. We therefore developed an approach in which the Cas9 protein is complexed with two synthetic gRNAs for precise excision of the intervening sequence (i.e. more controlled genome editing than what can be accomplished with a single gRNA). We directed these two gRNAs to intronic sequences for precise excision of exon 2, which encodes the V-set domain of CD33 that is recognized by all current CD33 therapeutics including GO. This approach eliminates exonic indels and protects engineered cells from CD33-targeted immunotherapy while maintaining expression of an exon 2-free variant of CD33 (CD33∆E2), which has previously been identified as natural isoform in human HSPCs.

Preliminary Results of the Stapled Peptide ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Two Phase IIa Dose Expansion Cohorts in Relapsed/Refractory TP53 Wild-Type Peripheral T-Cell Lymphoma
Andrei R. Shustov, MD
Poster
Session 624
Hall GH, San Diego Convention Center

Background: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of NHL with poor prognosis. Frontline therapy yields a 50-70% overall response rate, but the majority of pts will relapse, which translates to poor overall survival.

ALRN-6924, the first-in-class clinical stage stapled peptide, has been structurally stabilized (“stapled”) in an α-helical configuration, to mimic the inhibitor-binding region of the tumor suppressor protein, p53. By mimicking this region, ALRN-6924 binds the two most important endogenous inhibitors of p53, murine double minute-X (MDMX) and -2 (MDM2), thereby restoring p53’s ability to induce cell cycle arrest and apoptosis in TP53 wild-type (WT) cancer cells. ALRN-6924 is the first known synthetic agent to simultaneously target both of these important p53 inhibitors. A durable CR has been reported in a pt with an angioimmunoblastic subtype of PTCL who is part of the first-in-human study of ALRN-6924 (Meric-Bernstam et al., 2017), providing the rationale for two PTCL expansion cohorts.

The PTCL QW cohort is receiving treatment at the recommended Phase 2 dose (QWx3 every 28 days). Preclinical data suggest that more frequent dosing may enhance efficacy (Carvajal et al., 2018; Ng et al., 2018) and this hypothesis is being evaluated in a second PTCL cohort, treated TIWx1 every 21 days.

Limitations to Receiving Allogeneic Hematopoietic Cell Transplantation for Treatment of Acute Myeloid Leukemia: A Large Multi-Center Prospective Longitudinal Observational Study
Mohamed L. Sorror, MD
Poster
Session 613
Hall GH, San Diego Convention Center

Introduction: Acute myeloid leukemia (AML) is most frequently diagnosed in older patients (pts), whose median survival is less than 1 year. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. However, older pts often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. To this end, we designed a prospective, multi-center, longitudinal, observational study dating from first presentation of adult pts with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred.

Immunotherapy with T-Cells Engineered with a Chimeric Antigen Receptor Bearing a Human CD19-Binding Single Chain Variable Fragment for Relapsed or Refractory Acute Lymphoblastic Leukemia and B-Cell Non-Hodgkin Lymphoma
Jordan Gauthier, MD
Poster
Session 614
Hall GH, San Diego Convention Center

Background: We previously reported high response rates and durable remissions in patients (pts) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL; Turtle, JCI 2016) and non-Hodgkin lymphoma (NHL; Turtle, Sci Transl Med 2016) treated with CD19-specific chimeric antigen receptor T (CD19 CAR-T) cells. In a subset of pts, we identified CD8+ T cell responses to epitopes in the murine CD19-binding single chain variable fragment (scFv) of the CAR that could limit CAR-T cell persistence and responses to subsequent infusions. In an effort to reduce the potential for immune CAR-T cell rejection, the murine CD19-binding scFv of the CAR was replaced with a fully human scFv linked to 4-1BB and CD3z signaling domains (JCAR021; Sommermeyer, Leukemia 2017). Here we report the initial clinical results of immunotherapy with JCAR021.

Urinary Cross-Linked Carboxyterminal Telopeptide Decreases with Resolution of Painful Vaso-Occlusive Crises in Adults with Sickle Cell Disease - Results from the Sickle Cell Pain Markers (SCPM) Study
Oyebimpe O. Adesina, MD
Poster
Session 114
Hall GH, San Diego Convention Center

Introduction: Vaso-occlusive crises (VOCs), the most common acutely painful complication of sickle cell disease (SCD), presumably cause bone infarction. In a preclinical study that exposed sickle cell mice to repeated hypoxia-reperfusion stress—to recapitulate VOCs—the mice over-expressed osteoclast-driven bone resorption markers and suppressed osteoblast-mediated bone formation markers. We hypothesize that bone infarction stems from ongoing hemolysis and inflammation incurred during VOCs, and that the extent of bone degradation can be approximated by increases in concentrations of bone resorption markers in the plasma or urine of adults with SCD. We measured urinary levels of cross-linked carboxyterminal telopeptide (CTX-1, a bone resorption marker) in 52 adults with SCD, both during and after resolution of VOCs. We now report on the association between urinary CTX-1 concentrations and serum markers of hemolysis and inflammation.

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) Is Active and Well-Tolerated in Adults with Newly-Diagnosed Acute Lymphoblastic Leukemia/Lymphoma (ALL): Initial Results of a Phase II Trial
Ryan D. Cassaday, MD
Poster
Session 614
Hall GH, San Diego Convention Center

Background: HyperCVAD is used commonly in adult ALL but can be difficult for older or infirm patients (pts) to tolerate (JCO 2000, p. 547; Cancer 2008, p. 2097). At our center, only 50% who receive it reach a minimal residual disease negative (MRD-) state within 90 days (Am J Hematol 2018, p. 546). Lower-intensity options with ABL tyrosine kinase inhibitors (TKIs) yield high response rates in Philadelphia chromosome (Ph)+ disease, but long-term efficacy may be limited (Blood 2016, p. 774; ASH 2017, #99). DA-EPOCH is effective and relatively well-tolerated in high-grade lymphomas (NEJM 2013, p. 1915; Blood 2014, p. 2354). This prompted us to study DA-EPOCH as initial treatment of adult ALL.

Pembrolizumab in Combination with Standard RCHOP Therapy for Previously Untreated Diffuse Large B-Cell Lymphoma
Stephen D. Smith, MD
Poster
Session 626
Hall GH, San Diego Convention Center

Background: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) remains standard therapy for previously untreated diffuse large B-cell lymphoma (DLBCL). However, a substantial proportion of patients (pts) will relapse. The anti-PD-1 monoclonal antibody pembrolizumab has shown modest efficacy in previously treated DLBCL. We postulated that the first-line setting, with relatively intact host immunity and coexistence of malignant cells with T-cells in the microenvironment, may represent an opportunity for effective immune checkpoint inhibition. We carried out the first known prospective trial of anti-PD1 therapy with anthracycline chemotherapy in lymphoma, to evaluate the safety of this combination.

From Bone Marrow to Mobilized Peripheral Blood Stem Cells: The Circuitous Path to Clinical Gene Therapy for Fanconi Anemia
Pamela S. Becker, MD, PhD
Poster
Session 801
Hall GH, San Diego Convention Center

For decades, it has remained challenging to achieve long-term engraftment and correction of blood counts using gene-modified hematopoietic stem cells for Fanconi anemia. Toward this goal, our group conducted preclinical studies using a safety modified lentiviral vector encoding full-length cDNA for FANCA in normal and affected patient hematopoietic progenitor cells, and in a mutant mouse model that supported the IND for a gene therapy clinical trial for Fanconi anemia, complementation group A (NCT01331018). These studies led us to incorporate methods such as addition of N-acetylcysteine and hypoxic incubation during transduction.

The Alpha Emitter Astatine-211 Targeted to CD38 Can Eradicate Multiple Myeloma in Minimal Residual Disease Models
Shyril O'Steen, PhD
Poster
Session 652
Hall GH, San Diego Convention Center

Introduction: Multiple myeloma (MM) is considered incurable but patients achieving minimal-residual disease (MRD) negative status following treatment have significantly better overall and progression-free survival. MM is highly heterogeneous both between and within patients, limiting the curative potential of novel agents targeting specific pathways. However all MM is highly sensitive to radiation. The α-emitter astatine-211 (211At) deposits a very large amount of energy (~100 keV/μm) within a few cell diameters (50-90 μm) resulting in irreparable double strand DNA breaks, making 211At, targeted to MM cells, particularly suited to eliminating MRD. CD38 is expressed on malignant plasma cells regardless of mutational status, and CD38 monoclonal antibodies (mAbs) constitute a proven targeted therapy for MM but do not alone eradicate disease. We proposed that 211At conjugated to an anti-CD38 mAb could effectively eliminate MM MRD, and tested this hypothesis in cellular and murine models.

The Incidence of Thromboembolism for Lenalidomide Versus Thalidomide in Older Patients with Newly Diagnosed Multiple Myeloma
Ang Li, MD
Oral
Session 901
Room 8, San Diego Convention Center

Introduction: Chemotherapy backbones with immunomodulatory drugs have become the standard of care for the treatment of multiple myeloma (MM). Despite improved survival outcomes, thrombotic complications remain a concern especially in the older patients with co-morbidities. A meta-analysis showed that lenalidomide might be associated with lower rate of thromboembolism than thalidomide-containing regimen in patients with newly diagnosed MM with (0.7 vs. 2.6 per 100-patient-cycle) or without prophylaxis (0.8 vs. 4.1 per 100-patient-cycle) (JTH 2011;9:653). As thalidomide is still commonly used outside of the United States, it is important to understand if the thromboprophylaxis guideline is generalizable to all immunomodulatory drugs. However, no prior study has directly compared the thrombotic incidence between the two regimens while accounting for confounders. In the current propensity score weighted study, we have examined the incidence of venous (VTE) and arterial (ATE) thromboembolism and survival for older patients with newly diagnosed MM treated with lenalidomide- versus thalidomide-containing regimen.

Use of Gemtuzumab Ozogamicin for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML) or Acute Promyelocytic Leukemia (APL) in an Expanded Access Setting at Our Cancer Consortium
Kelda M. Gardner, PA-C
Poster
Session 615
Hall GH, San Diego Convention Center

Introduction: Gemtuzumab ozogamicin (GO, MylotargTM) was re-approved by the FDA and has been commercially available since September 2017. Prior to re-approval, adults and children with relapsed/refractory AML or APL were treated with GO obtained through an expanded access program under an institutional IND at our Cancer Consortium: Fred Hutchinson Cancer Research Center (FHCRC), the University of Washington Medical Center (UWMC), Seattle Children’s Hospital (SCH), and the Seattle Cancer Care Alliance (SCCA).

Management of Mucositis with the Use of Leucovorin As Adjunct to Pralatrexate in Treatment of Peripheral T-Cell Lymphomas (PTCL) – Results from a Prospective Multicenter Phase 2 Clinical Trial
Andrei R. Shustov, MD
Poster
Session 624
Hall GH, San Diego Convention Center

Background: A frequent complication of Pralatrexate therapy is development of oral mucositis. In a recent pivotal trial of pralatrexate (PROPEL, O’Connor et al. J Clin Onc 2011) the incidence of ≥ Grade 2 mucositis was 52%, occurring primarily in the first treatment cycle. Mucositis often leads to dose reduction or omission and possibly, diminished efficacy of pralatrexate in relapsed/refractory (R/R) PTCL. Leucovorin (d,l-folinic acid) is an approved rescue therapy for high-dose methotrexate (MTX) therapy, mitigating gastrointestinal lining, and bone marrow cell toxicity and has been used adjunctively with pralatrexate to manage mucositis. The objective of this prospective Phase 2, single-arm study was to evaluate the effect of leucovorin on the incidence of pralatrexate-induced mucositis in patients with R/R PTCL, including primary cutaneous T-cell lymphomas.

Early Response Data for Pediatric Patients with Non-Hodgkin Lymphoma Treated with CD19 Chimeric Antigen Receptor (CAR) T-Cells
Julie Rivers, MD
Poster
Session 626
Hall GH, San Diego Convention Center

Background:Pediatric patients with relapsed or refractory CD19+non-Hodgkin lymphoma (NHL) have poor outcomes despite use of chemotherapy and hematopoietic stem cell transplant (HSCT). Clinical trials of CD19 CAR T-cells have demonstrated efficacy in salvaging adult patients with relapsed and refractory NHL.

Ibrutinib Is Effective in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma: Results from a Prospective Phase II Study
Solomon A. Graf, MD
Poster
Session 626
Hall GH, San Diego Convention Center

Background: Relapsed or refractory (R/R) transformed indolent B-cell non-Hodgkin lymphoma (iB-NHL) is associated with a poor prognosis. Unfortunately, there is little prospective data using novel agents, including kinase inhibitors, since trials tend to specifically exclude transformed disease. To address this question we evaluated single agent ibrutinib in patients with R/R transformed iB-NHL.

Eligibility for Car-T Trials: An Analysis of Selection Criteria and Survival Outcomes in Chemorefractory DLBCL
Stephen D. Smith, MD
Poster
Session 624
Hall GH, San Diego Convention Center

Background: Chemorefractory diffuse large B-cell lymphoma (DLBCL) is associated with poor outcomes. Recent Car-T therapy trials, including Zuma-1 which led to the first FDA approval of Car-T for DLBCL (Neelapu NEJM), have shown sustained complete remission, disease control, and long-term survival in a proportion of patients. As with all trials, results must be interepreted in context of study definitions and eligibility parameters. While selection bias is often discussed, little published data regarding specific eligibility requirements on accrual of DLBCL trials exists. To better understand factors influencing Car-T trial eligibility in DLBCL, and context for observed survival rates in Car-T trials, we examined chemorefractory DLBCL patients seen from 2011-2015 at our center, applying key eligibility criteria from Zuma-1 and describing likely reasons for trial exclusion.

The First Investigational Factor VIII Therapy to Break Through the VWF Ceiling in Hemophilia A, with Potential for Extended Protection for One Week or Longer
Barbara A. Konkle, MD
Oral
Session 322
Room 30D, San Diego Convention Center

Introduction: The standard of care for patients with severe hemophilia A is prophylactic factor VIII (FVIII) replacement. Conventional recombinant FVIII products are efficacious but require frequent administration because of their short half-life, which reflects the dependence of FVIII on von Willebrand factor (VWF). Recombinant FVIII Fc fusion protein (rFVIIIFc) provides an extended dosing interval, as well as joint protection and improved quality of life (Oldenburg et al, Haemophilia, 2018; Wang et al, Blood, 2016), with a well-characterized safety profile. While rFVIIIFc reduces the required administration frequency, longer prophylactic dosing intervals that also offer maximum overall protection are still an unmet need for patients with severe hemophilia A. Increasing the half-life of rFVIII is ultimately dependent upon decoupling FVIII and endogenous VWF.

Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma
Damian J. Green, MD
Oral
Session 653
Ballroom 20D, San Diego Convention Center

Background: Despite advances in the treatment of multiple myeloma (MM) almost all patients relapse and high risk features continue to portend a short median survival. The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in MM, but the durability of response has not been established. The infusion of genetically modified CD8+ and CD4+ T cells of a defined composition facilitates the evaluation of each subset’s function and has contributed to reproducible efficacy and safety in clinical trials with CD19-specific CAR T cells. In this phase I first-in-human study employing a human scFv containing BCMA CAR T cell construct, we report rapid and deep objective responses at a low CAR T cell dose level (5 x 107) suggesting that construct specific features and differences in product formulation may substantially impact efficacy.

Speakers
More than 50 members of our leading-edge research team will be sharing their latest findings. Here are some of the highlights.
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.

Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma
Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma : Session 653
Oral
Ballroom 20D, San Diego Convention Center

Background: Despite advances in the treatment of multiple myeloma (MM) almost all patients relapse and high risk features continue to portend a short median survival. The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in MM, but the durability of response has not been established. The infusion of genetically modified CD8+ and CD4+ T cells of a defined composition facilitates the evaluation of each subset’s function and has contributed to reproducible efficacy and safety in clinical trials with CD19-specific CAR T cells. In this phase I first-in-human study employing a human scFv containing BCMA CAR T cell construct, we report rapid and deep objective responses at a low CAR T cell dose level (5 x 107) suggesting that construct specific features and differences in product formulation may substantially impact efficacy.

Oyebimpe O. Adesina, MD
  • Hematologist Oncologist, Seattle Cancer Care Alliance

Monoclonal, gammopathy, chronic myeloid leukemia, essential thrombocytosis, myeloproliferative syndrome, polycythemia vera, anemia, cytopenia, sickle cell disease, elevated count on CBC and thrombosis. 

Urinary Cross-Linked Carboxyterminal Telopeptide Decreases with Resolution of Painful Vaso-Occlusive Crises in Adults with Sickle Cell Disease - Results from the Sickle Cell Pain Markers (SCPM) Study
Urinary Cross-Linked Carboxyterminal Telopeptide Decreases with Resolution of Painful Vaso-Occlusive Crises in Adults with Sickle Cell Disease - Results from the Sickle Cell Pain Markers (SCPM) Study : Session 114
Poster
Hall GH, San Diego Convention Center

Introduction: Vaso-occlusive crises (VOCs), the most common acutely painful complication of sickle cell disease (SCD), presumably cause bone infarction. In a preclinical study that exposed sickle cell mice to repeated hypoxia-reperfusion stress—to recapitulate VOCs—the mice over-expressed osteoclast-driven bone resorption markers and suppressed osteoblast-mediated bone formation markers. We hypothesize that bone infarction stems from ongoing hemolysis and inflammation incurred during VOCs, and that the extent of bone degradation can be approximated by increases in concentrations of bone resorption markers in the plasma or urine of adults with SCD. We measured urinary levels of cross-linked carboxyterminal telopeptide (CTX-1, a bone resorption marker) in 52 adults with SCD, both during and after resolution of VOCs. We now report on the association between urinary CTX-1 concentrations and serum markers of hemolysis and inflammation.

Pamela S. Becker, MD, PhD
  • Attending Physician, Seattle Cancer Care Alliance
  • Professor, Hematology Division, University of Washington School of Medicine

Plasma cell leukemia, acute myeloid leukemia, acute promyelocytic leukemia, acquired aplastic anemia, Faconi anemia, chronic myeloid leukemia, myelodysplastic syndrome and Gaucher disease.

From Bone Marrow to Mobilized Peripheral Blood Stem Cells: The Circuitous Path to Clinical Gene Therapy for Fanconi Anemia
From Bone Marrow to Mobilized Peripheral Blood Stem Cells: The Circuitous Path to Clinical Gene Therapy for Fanconi Anemia : Session 801
Poster
Hall GH, San Diego Convention Center

For decades, it has remained challenging to achieve long-term engraftment and correction of blood counts using gene-modified hematopoietic stem cells for Fanconi anemia. Toward this goal, our group conducted preclinical studies using a safety modified lentiviral vector encoding full-length cDNA for FANCA in normal and affected patient hematopoietic progenitor cells, and in a mutant mouse model that supported the IND for a gene therapy clinical trial for Fanconi anemia, complementation group A (NCT01331018). These studies led us to incorporate methods such as addition of N-acetylcysteine and hypoxic incubation during transduction.

High Throughput Drug Screening of Leukemia Stem Cells Reveals Resistance to Standard Therapies and Sensitivity to Other Agents in Acute Myeloid Leukemia
High Throughput Drug Screening of Leukemia Stem Cells Reveals Resistance to Standard Therapies and Sensitivity to Other Agents in Acute Myeloid Leukemia : Session 604
Oral
Grand Hall D, Manchester Grand Hyatt San Diego

Background: Leukemia stem cells (LSCs) play a critical role in AML propagation and relapse. Other investigators have also highlighted unique gene expression profiles for the leukemia stem cell population. Here we compared the results of in vitro drug sensitivity testing against a custom panel of drugs and drug combinations for blast populations vs. leukemia stem cell populations derived from the same patients, as well as mutation analysis for a panel of 194 recurrently mutated genes in AML.

Ryan D. Cassaday, MD
  • Hematologist Oncologist, Seattle Cancer Care Alliance
  • Assistant Professor, Division of Hematology, University of Washington School of Medicine

Acute lymphoblastic leukemia and cellular immunotherapy
 

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) Is Active and Well-Tolerated in Adults with Newly-Diagnosed Acute Lymphoblastic Leukemia/Lymphoma (ALL): Initial Results of a Phase II Trial
Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) Is Active and Well-Tolerated in Adults with Newly-Diagnosed Acute Lymphoblastic Leukemia/Lymphoma (ALL): Initial Results of a Phase II Trial : Session 614
Poster
Hall GH, San Diego Convention Center

Background: HyperCVAD is used commonly in adult ALL but can be difficult for older or infirm patients (pts) to tolerate (JCO 2000, p. 547; Cancer 2008, p. 2097). At our center, only 50% who receive it reach a minimal residual disease negative (MRD-) state within 90 days (Am J Hematol 2018, p. 546). Lower-intensity options with ABL tyrosine kinase inhibitors (TKIs) yield high response rates in Philadelphia chromosome (Ph)+ disease, but long-term efficacy may be limited (Blood 2016, p. 774; ASH 2017, #99). DA-EPOCH is effective and relatively well-tolerated in high-grade lymphomas (NEJM 2013, p. 1915; Blood 2014, p. 2354). This prompted us to study DA-EPOCH as initial treatment of adult ALL.

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. 

Prolonged Lenalidomide Therapy in Multiple Myeloma Patients Does Not Impact Autologous PBSC Mobilization: A Single Center Retrospective Analysis
Prolonged Lenalidomide Therapy in Multiple Myeloma Patients Does Not Impact Autologous PBSC Mobilization: A Single Center Retrospective Analysis : Session 711
Oral
Grand Hall A, Manchester Grand Hyatt San Diego

Background: Autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma (MM). Typically, patients receive several cycles of induction therapy to achieve appropriate cytoreduction prior to ASCT. Since the introduction of lenalidomide into induction therapy, there have been conflicting reports about its impact on subsequent autologous peripheral blood stem cell (PBSC) mobilization. Early reports showed a trend of patients failing PBSC mobilization and collection after lenalidomide when granulocyte colony stimulating factor (GCSF) was employed as a single agent. More recent reports suggested that using chemotherapy in combination with growth factors including plerixafor can overcome failures of mobilization. To address these conflicting reports, we evaluated the impact of prior lenalidomide in a large cohort of MM patients undergoing mobilization and collection at a tertiary stem cell transplant center.

Clinical Trials
Phase II Study of Rituximab Plus Pembrolizumab (MK-3475) in Subjects with Relapsed Follicular and Diffuse Large B-Cell Lymphoma
Stephen Douglas Smith, MD
NCT03401853

This phase II trial studies how well rituximab and pembrolizumab work in treating patients with follicular lymphoma or diffuse large B cell lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread.
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 Response-Adapted Clinical Trial of Weekly Carfilzomib with or without Rituximab for Waldenstrom's Macroglobulinemia and Marginal Zone Lymphoma
Stephen Douglas Smith, MD
NCT03269552

This phase II trial studies how well carfilzomib with or without rituximab work in treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma that is previously untreated, has come back, or does not respond to treatment. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving carfilzomib alone when disease is responding or with rituximab when disease is not responding may work better in treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma.
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 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 LY3039478 (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.
Impact of Treatment Intensity on Survival, Quality of Life, and Resource Utilization in Medically Less Fit Adults with Acute Myeloid Leukemia and Analogous Myeloid Neoplasms: A Randomized Pilot Study
Anna B. Halpern, MD
NCT03012672

This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid leukemia or myeloid neoplasm. Drugs used in chemotherapy, such as cladribine, cytarabine, and mitoxantrone, 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. It is not yet known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may work better in treating patients with newly diagnosed acute myeloid leukemia.

A Feasibility Study of 'Early' Allogenic Hematopoietic Cell Transplantation for Relapsed or Refractory High-Grade Myeloid Neoplasm

Mary-Beth Percival, MD
NCT02756572

This clinical trial studies how well early stem cell transplantation works in treating patients with high-grade myeloid neoplasms that has come back after a period of improvement or does not respond to treatment. 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. Giving chemotherapy before a donor peripheral blood cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient?s immune cells and help destroy any remaining cancer cells. Early stem cell transplantation may result in more successful treatment for patients with high-grade myeloid neoplasms.
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)
Marie E. Bleakley, MD
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.
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, MD, PhD
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.
CLBH589DUS108T: Panobinostat with Carfilzomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Correlation with In Vitro Chemosensitivity Testing
Pamela S. Becker, MD, PhD
NCT03256045

This phase II trial studies how well panobinostat, carfilzomib and dexamethasone work in treating patients with multiple myeloma that has come back or does not respond to treatment. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carfilzomib and dexamethasone, 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. Using multiple myeloma cells from patients' blood samples, the researchers will do laboratory tests to look at how well each of the drugs, alone and in different combinations, kill multiple myeloma cells. If the laboratory tests work well, they may be used in the future to help plan treatment for future patients.

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