Innovative approaches to lymphoma: clinical trials including CAR T-cell therapy, transplant, bispecific antibodies, novel kinase and checkpoint inhibitors

 

SCCA lymphoma specialists offer unique options  

As survival rates for lymphoma are improving, the first therapy is typically the most effective and important. But patients may need more than one therapy. SCCA has one of largest and most comprehensive multidisciplinary lymphoma teams in the nation, and the largest team in the Northwest. Our team can offer both longitudinal direct or collaborative care along with the most innovative clinical trial offerings for patients with untreated or relapsed lymphoma. We can also provide guidance and continuous input through related therapies such as transplant and CAR T. 

Lymphoma: incorporating CAR T therapies earlier than ever before 

SCCA is the only facility in the Northwest — and one of the first in the U.S. — to offer two FDA-approved CAR T-cell therapies, Yescarta and Kymriah, for patients with relapsed or refractory aggressive large B-cell lymphoma. And we have dozens of active and upcoming clinical trials testing new approaches and therapies. 
 
The current standard of care for many lymphomas places CAR T-cell therapy as a late or final option for treatment, usually following one failed course of chemotherapy and a bone marrow transplant. Clinical trials are offering CAR T-cell therapy earlier to see if it can improve outcomes.  

“Patients who receive CAR T-cells with less disease burden appear to have less toxicity and also have better outcomes, with better survival and a better long-term remission rate,” says David Maloney, MD, PhD, who serves as Medical Director of Cellular Immunotherapy at SCCA. “If a patient is failing standard therapy, it’s important to consider if there are any clinical trials of these therapies, as early as possible.” 

Lymphoma: transplants remain a key option for many 

SCCA and its alliance partner, Fred Hutchinson Cancer Research Center, pioneered many groundbreaking lymphoma treatments, including stem cell and bone marrow transplants (BMT). The newer immunotherapies may decrease some types of transplant, but also may increase the ability for some patients with leukemia to receive transplants.  

“Transplants revolutionized care,” says Marco Mielcarek, MD, PhD, who serves as Medical Director of SCCA’s Adult Blood and Marrow Transplant Program. “It’s exciting to have alternatives for a growing number of patients, and my team works closely with physicians across SCCA to explore those alternatives and make sure each patient gets matched with the therapy or clinical trial that’s right for them.”  

Clinical trials that challenge the status quo 

SCCA has numerous trials that challenge the status quo including multiple non-chemo oral treatment options for patients with newly diagnosed or recurrent lymphoma. Some trials incorporate immunotherapy as part of the first treatment for lymphoma and others include treatments that “link” tumor killing T-cells to lymphoma cells by a simple infusion or include novel immunostimulatory agents designed to further leverage the immune system to fight the cancer. SCCA promptly screens patients for appropriate trials and presents unique options, alongside the standard treatments. 

One Phase 2 study gives patients Yescarta as soon as their cancer shows signs of progressing during chemotherapy.  
 
“If patients with high risk lymphoma don’t respond quickly to their initial therapy, we can quickly offer a commercially-approved CAR even in their first line of therapy,” Dr. Maloney says.  

We’re also offering a Phase 1/2 study of a third-generation therapy — the only one targeting the CD20 antigen, rather than CD19 — to see whether it’s even less toxic than existing CARs. 

A third, Phase 3 study (NCT03575351) poses the most direct comparison between the current standard of care and early delivery of immunotherapy. All patients in this study have relapsed or refractory lymphoma following an initial course of chemotherapy. One group will move on to salvage chemotherapy and, if possible, BMT. The other group will be treated with JCAR017 — a new CAR T-cell based therapy, based on research at Fred Hutch, that provides an equal amount of modified CAR CD4 and CD8 and modified T-cells. The two patient groups will be compared across 14 metrics, with event-free survival as the primary outcome. 

So far, JCAR017 (lisocabtagene marileucel) has proven to be effective with less severe toxicity. 

“Because of our CAR T-cell center’s experience, we have been able to treat most of our patients on an outpatient basis, and 30 to 40 percent of patients do not require hospitalization during their course of treatment,” Dr. Maloney says. “These results could be practice-changing.”

Unique expertise = better outcomes 

Physicians and researchers across SCCA, UW Medicine and Fred Hutch played a key role in developing multiple treatments for lymphoma including CAR T-cell therapies and are constantly devising ways to make these therapies even more effective and less toxic. We’ve also guided more patients through immunotherapy treatment than almost any center in the world. This gives us the expertise to know which therapies are right for a particular patient, to identify complications as early as possible, and to deliver care that gives each patient the best opportunity for a good outcome.  

“When a patient is referred to us, we team up with physicians across hematologic malignancies, cell therapy and transplant to identify the best therapy and/or clinical trial,” Dr. Mielcarek says. “That team also includes the referring provider — we partner with them so we can deliver the best possible outcome and return the patient to their care as soon as possible.”

Contact our teams for consults or referrals.    

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. Clinical trial A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis or treatment of a disease. 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. Infusion An injection of medications or fluids into a vein over a period of time. 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. 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. Sign In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. Some examples of signs are fever, swelling, skin rash, high blood pressure and high blood glucose. Standard care A treatment or other intervention currently being used and considered to be of proven effectiveness based on past studies. Standard care A treatment or other intervention currently being used and considered to be of proven effectiveness based on past studies. Standard treatment A treatment or other intervention currently being used and considered to be of proven effectiveness based on past studies. Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.