Improving outcomes for mantle cell lymphoma

By SCCA staff · February 22, 2021

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.

Chimeric antigen receptor T-cell therapy A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then, in the laboratory, the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells. This special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Chimeric antigen receptor T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer. Also called CAR T-cell therapy. Lymphoma Cancer that begins in the cells of the immune system. There are two basic categories of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas. Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer. Refractory In medicine, refractory disease is a disease or condition that does not respond to treatment. Relapse The recurrence (return) of disease after an apparent recovery.

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.
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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.
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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.
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“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.”

Allogeneic stem cell transplant Uses bone marrow or stem cells from a related or unrelated donor whose tissue type closely matches the patient’s. Replaces blood-forming cells that have been destroyed by disease or cancer treatment. Uses bone marrow or stem cells from a donor whose tissue type closely matches the patient’s to replace blood-forming cells that have been destroyed by disease or cancer treatment. This can be from a related or unrelated donor. Antibody A protein made by immune system cells and released into the blood. Antibodies defend the body against foreign substances, such as bacteria. Antigen A foreign substance, such as bacteria, that causes the body’s immune system to respond by making antibodies. Antibodies defend the body against antigens. B-cell lymphoma A type of cancer that forms in B cells (a type of immune system cell). B-cell lymphomas may be either indolent (slow-growing) or aggressive (fast-growing). Most B-cell lymphomas are non-Hodgkin lymphomas. A type of cancer that forms in B cells (a type of immune system cell). B-cell lymphomas may be either indolent (slow-growing) or aggressive (fast-growing). Most B-cell lymphomas are non-Hodgkin lymphomas. There are many different types of B-cell non-Hodgkin lymphomas. These include Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Prognosis and treatment depend on the type and stage of the cancer. Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Bone marrow transplant The process of treating disease with high doses of chemotherapy, radiation therapy or both. Bone marrow or peripheral blood stem cells are given after treatment to help the body make more blood cells. The process of treating disease with high doses of chemotherapy, radiation therapy or both. Because this treatment destroys the bone marrow’s ability to produce blood cells, bone marrow or peripheral blood stem cells are given after treatment to help the body make more blood cells. Chemotherapy Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may be given alone or with other treatments. Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection, infusion or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy or biologic therapy. Chimeric antigen receptor T-cell therapy A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then, in the laboratory, the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells. This special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Chimeric antigen receptor T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer. Also called CAR T-cell therapy. Grade In cancer, a grade is a description of a tumor based on how abnormal the cancer cells and tissue look under a microscope and how quickly the cancer cells are likely to grow and spread. In cancer, a grade is a description of a tumor based on how abnormal the cancer cells and tissue look under a microscope and how quickly the cancer cells are likely to grow and spread. Low-grade cancer cells look more like normal cells and tend to grow and spread more slowly than high-grade cancer cells. Grading systems are different for each type of cancer. They are used to help plan treatment and determine prognosis. Also called histologic grade and tumor grade. Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies. Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies. Lymphoma Cancer that begins in the cells of the immune system. There are two basic categories of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas. Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer. Mantle cell lymphoma An aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma that usually occurs in middle-aged or older adults. An aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma that usually occurs in middle-aged or older adults. It is marked by small- to medium-size cancer cells that may be in the lymph nodes, spleen, bone marrow, blood and gastrointestinal system. Non-Hodgkin lymphoma Any of a large group of cancers of the lymphocytes (white blood cells). Non-Hodgkin lymphomas can occur at any age and are often marked by lymph nodes that are larger than normal, fever and weight loss. Any of a large group of cancers of lymphocytes (white blood cells). Non-Hodgkin lymphomas can occur at any age and are often marked by lymph nodes that are larger than normal, fever and weight loss. There are many different types of non-Hodgkin lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow-growing) types, and they can be formed from either B cells or T cells. B-cell non-Hodgkin lymphomas include Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma and mantle cell lymphoma. T-cell non-Hodgkin lymphomas include mycosis fungoides, anaplastic large cell lymphoma and precursor T-lymphoblastic lymphoma. Lymphomas that occur after bone marrow or stem cell transplantation are usually B-cell non-Hodgkin lymphomas. Prognosis and treatment depend on the stage and type of disease. Also called NHL. Oncologist A physician who has special training in diagnosing and treating cancer. Some oncologists specialize in a particular type of cancer treatment, such as treating cancer with radiation. A physician who has special training in diagnosing and treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. Refractory In medicine, refractory disease is a disease or condition that does not respond to treatment. Relapse The recurrence (return) of disease after an apparent recovery. Remission A decrease in, or disappearance of, signs and symptoms of cancer. A decrease in, or disappearance of, signs and symptoms of cancer. In partial remission, some (but not all) signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body. Side effects A problem that occurs when treatment affects healthy tissues or organs. Some side effects of cancer treatment are nausea, vomiting, fatigue, pain, decreased blood cell counts, hair loss and mouth sores. Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells. T cell A type of white blood cell. T cells are part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer. A type of white blood cell. T cells are part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer. Also called T lymphocyte and thymocyte.

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mantle cell lymphoma

clinical trials

Lymphoma

CAR T cell

bone marrow transplant

immunotherapy

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