Improving outcomes for mantle cell lymphoma

Mantle cell lymphoma (MCL) is rare and difficult to manage, since it can range from a slow-growing disease to an aggressive form that is difficult to control. Fortunately, a new wave of treatments and clinical trials is bringing more options to patients with MCL.

These innovations include Brexucabtagene Autoleucel (Tecartus), a CAR T-cell therapy newly approved by the FDA for relapsed or refractory MCL, as well as clinical trials that investigate other novel approaches. These advances are especially significant for patients with relapsed or refractory MCL.

Seattle Cancer Care Alliance (SCCA) treats more MCL patients than almost any other center in the Pacific Northwest region and offers one of the nation’s most robust portfolios of standard treatments and clinical trials, in partnership with Fred Hutchinson Cancer Research Center and University of Washington Medical Center (UWMC). The portfolio includes trials of new targeted treatments and immunotherapies that could someday replace bone marrow transplants, which are commonly used as part of first-line treatment of MCL.

“In many patients, treating MCL has meant extrapolating from other lymphomas, but new treatments specific to MCL have arrived and are changing the treatment landscape quickly and survival rates are improving,” says Stephen Smith, MD, an SCCA oncologist who specializes in lymphoma and other blood disorders. Dr. Smith plays a key role in developing and testing new therapies in his role as an Associate Professor with Clinical Research Division at the Fred Hutchinson Cancer Research Center.

At SCCA, all new patient cases are discussed by a multi-disciplinary team of lymphoma experts, including physicians specializing in medical oncology, hematology, radiation oncology, neuro-oncology, transplant, immunotherapy, hematopathology, and other specialties, to ensure patients have the best clinical care and research opportunities.

CAR T-cell therapy for relapsed/refractory MCL

SCCA is among a small handful of centers in the Pacific Northwest authorized to offer Tecartus, which can provide deep remissions, even in patients for whom all other treatments failed. In the recent ZUMA-2 study, 85% of participants with relapsed or refractory MCL responded to Tecartus, with 59% achieving complete remission and 26% achieving partial remission. Tecartus treatment usually involves a two- to three-month stay at SCCA with treatment in the Bezos Family Immunotherapy Clinic.

“This is a significant improvement because, historically, second- or third-line treatments for mantle cell lymphoma haven't achieved complete remission in most patients,” Dr. Smith says.

The study also found that 15% of patients developed grade 3 or higher cytokine release syndrome, and 31% developed grade 3 or higher neurological toxicities. These effects are similar to those reported in studies of other anti-CD19 CAR T-cell therapies in patients with aggressive B-cell lymphoma.

SCCA’s extensive experience with CAR T-cell therapies translates to expertise in minimizing these side effects and quickly detecting and treating them when they do arise. In partnership with Fred Hutch, SCCA played a key role in developing CAR T-cell therapies and has guided more patients through CAR T-cell treatment than many centers in the world. Additionally, SCCA is continually devising ways to improve CAR T-cell therapies and extend their reach.

“We suspect Tecartus might turn out to be useful earlier in the course of disease, and we are carefully assessing which subgroups should consider it after first- or second-line therapy,” Dr. Smith says.

Expanding MCL options via clinical trials

SCCA offers access to an array of clinical trials and treatments that go beyond Tecartus and expands options for patients with early- and later-stage MCL. Based on years of experience with MCL and clinical research, the specialists at SCCA will match patients with the therapy that’s right for them. Available clinical trials include but are not limited to:

  • A Phase 3 trial that compares efficacy of Rituximab combined with either Zanubrutinib (a next-generation BTK inhibitor) or Bendamustine (an alkylating agent) in patients who have not received previous treatments and are not eligible for a stem cell transplant. This trial offers a new potential front-line treatment option for older patients and those with comorbidities who have limited options. It also offers the possibility of improving outcomes without chemotherapy.
    View trial
     
  • A Phase 1/2 study of autologous T cells engineered to target the CD20 antigen on the surface of B-cell non-Hodgkin lymphomas. This trial may help advance the use of CAR T-cell therapy in patients with relapsed or refractory lymphomas, including MCL.
    View trial
     
  • A Phase 1 trial of IgM-2323 in adult patients with relapsed or refractory B-cell non-Hodgkin lymphoma. This study tests an engineered bispecific IgM antibody for patients with CD20-positive cancers. Preclinical studies showed encouraging results in aggressive lymphomas and against some tumors that are resistant to Rituximab. Some MCL patients qualify for the first leg of this study.
    View trial

“If patients aren't candidates for Tecartus, we can offer several other options and guide them through treatment in a way that delivers the best opportunity for a good outcome,” Dr. Smith says.

The role of bone marrow transplant in MCL treatment

Autologous bone marrow transplants remain a viable treatment option for MCL patients who are relatively young and fit, with the goal of achieving long-term remission.

“The standard philosophy for those patients is still to treat MCL very heavily the first time around in hopes of getting a decade or more of remission for some patients,” Dr. Smith says. “We usually follow that approach until we have trials telling us another method is better, but all patients deserve—and are offered—personalized treatment plans based on their MCL subtype, health and philosophy.”

In selected cases, autologous transplants can also be used as a second- or third- line treatment. Stemming from Fred Hutch’s pioneering work in the development of bone marrow transplants, SCCA has a very active transplant program for patients as needed.

Allogeneic transplant also remains a viable option for certain subsets of MCL patients, but Dr. Smith is hopeful that CAR T-cell therapies and/or other innovative approaches can eventually reduce the need for transplants.

“We’re going to continue pursuing advances and keeping a close eye on the Tecartus long-term follow-up data,” he says, “and will hopefully be able to offer transplant alternatives that are curative and less toxic.”