Immunotherapy for Lymphoma, Multiple Myeloma, and Leukemia: What’s New?

Immunotherapy has dramatically improved the treatment of blood cancers including lymphomas, multiple myeloma, and certain forms of leukemia. 

Dana-Farber experts have been at the forefront of research into immunotherapies for blood cancer, particularly in the discovery and development of immune checkpoint inhibitors such as pembrolizumab to treat cancer. Their ongoing investigations are shaping how these medicines and other immunotherapies will be used to treat blood cancers in the future. 

 These immunotherapies include: 

• Immune checkpoint inhibitors, which are used in the treatment of some lymphomas. They unleash the immune system by removing the masks cancers use to hide from immune cells. 

• Bispecific antibodies, which are used in the treatment of certain forms of lymphoma, multiple myeloma, and leukemia. They help bring anti-cancer immune cells called T cells closer to cancer cells and activate them so the T cells can mount an attack against the cancer. 

• CAR T-cell therapies, which are used in the treatment of certain forms of lymphoma, multiple myeloma, and leukemia. They deliver T cells that are engineered to attack a patient’s cancer. 

• Combination therapies, which might include multiple immunotherapies, combinations of an immunotherapy with other therapies, and various sequences of therapies. 

“Immune checkpoint inhibitors have completely transformed oncology; those, and more recently other forms of immunotherapy such as CAR T-cell therapies and bispecific antibodies, are delivering substantial improvements for patients,” says Philippe Armand, MD, PhD, chief of the Division of Lymphoma at Dana-Farber Cancer Institute. “Our primary efforts now are to move these treatments into earlier lines of therapy where they have the potential to have an even larger impact.”  

Immunotherapy for lymphoma 

The first game-changing immunotherapy for lymphoma, a cancer of the lymphatic system, was rituximab, a monoclonal antibody therapy introduced more than 25 years ago. Rituximab is still in use today, along with multiple new and sophisticated immunotherapies for the treatment of a range of lymphomas. 

Immune checkpoint inhibitors for Hodgkin lymphoma 

The immune checkpoint inhibitors nivolumab and pembrolizumab were first approved in 2016 and 2017 for patients with advanced Hodgkin lymphoma that had relapsed after stem cell transplant or after several lines of treatment. Since then, the use of these medicines has expanded, and they are now used even in frontline therapy for certain patients.  

“Recently the goal,” says Armand, “has been to bring these therapies into front-line treatment, where they have the potential to increase the cure rate for this disease.” 

Immune checkpoint inhibitors are also approved for a rare and aggressive form of non-Hodgkin lymphoma called primary mediastinal B-cell lymphoma.  

The evidence suggesting that these medicines would be a match for these diseases came from observations in the Dana-Farber lab of Margaret Shipp, MD. Dana-Farber investigators also helped run the clinical trials that led to approvals of these medicines. 

CAR T-cell therapies for non-Hodgkin lymphoma 

CAR T-cell therapy was first approved for non-Hodgkin lymphoma in 2017. That approval was for the treatment of relapsed/refractory large B-cell lymphoma. Since then, several other CAR T-cell therapies have been approved for other non-Hodgin lymphomas, including follicular lymphoma and mantle cell lymphoma.  The use of these therapies has also moved earlier, to the second line of treatment, for higher risk B-cell lymphomas. These therapies have become a very important part of the treatment approach for aggressive lymphomas.  

Dana-Farber investigators, led by Caron Jacobson, MD, MMSc, participated and led some of the key trials of CAR-T cells in lymphoma and established the clinical infrastructure required for centers to deliver these novel therapies safely both for in-patient and out-patient treatment. 

Bispecific antibodies for lymphoma 

Several bispecific antibodies are also approved for certain non-Hodgkin lymphomas. Dana-Farber researchers are investigating combinations of bispecific antibodies in earlier lines of treatment and for other forms of lymphoma including follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma, and large cell lymphoma. 

Learn more about Dana-Farber clinical trials for lymphoma. 

Dana-Farber investigators led by Jennifer Crombie, MD, have also helped established the clinical infrastructure needed to deliver bispecific antibodies safely, resulting in the improvement of access to these medicines in community care centers.  

“The ability to deliver these new therapies like bispecific antibodies and cellular therapies safely required intensive research and planning,” says Armand. “Our team has set the standards for others to follow in terms of training staff and establishing the required systems.” 

Immunotherapies for multiple myeloma 

Both CAR T-cell therapies and bispecific antibodies have changed the treatment of multiple myeloma, a cancer of plasma cells in the blood. 

CAR T-cell therapies have become standard of care for many patients with multiple myeloma and have moved earlier in treatment, with some patients receiving CAR T-cell therapies as a second line of treatment. A large clinical study is also evaluating the use of CAR T-cell therapy as a replacement for stem cell transplant in patients with newly diagnosed multiple myeloma.  

Several bispecific antibodies are also approved for treatment of multiple myeloma after a patient has relapsed. 

“These immunotherapies have changed our approach to treatment,” says Adam Sperling, MD, PhD, associate director of Basic and Correlative Science, Multiple Myeloma and Cell Therapies. “The big question going forward is whether or not there are patients that can be cured potentially by combining different immunotherapies with our standard agents.” 

New ideas being studied in Dana-Farber laboratories and early-stage clinical trials include: 

• Trispecific antibodies that target more than one marker on the cancer and one marker on a T cell,  

• Combining bispecific antibodies with CAR T-cell therapy,  

• Efforts to enhance or extend the effects of CAR T-cell therapies with additional agents.  

Learn more about Dana-Farber clinical trials for multiple myeloma. 

Immunotherapies for leukemia 

Immunotherapies have shown the most progress so far for patients with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Leukemia affects white blood cells or cells that develop into white blood cells. 

Bispecific antibodies for ALL 

The bispecific antibody blinatumomab has transformed the treatment of ALL. Blinatumomab is a subtype of bispecific antibody called a bispecific T-cell engager; the two work similarly but differ in their structure.  

Blinatumomab was initially approved for the treatment relapsed/refractory Philadelphia-chromosome-negative ALL in 2014. Since then, in part thanks to clinical trials at Dana-Farber, its use has expanded. It is now approved for relapsed/refractory Philadelphia-chromosome positive disease, and for newly diagnosed patients who are in remission after initial chemotherapy, called consolidation therapy, whether they have microscopic signs of disease or not.  

Dana-Farber investigators are exploring its use in more scenarios, such as in combination with other therapies.  

CAR T-cell therapies for ALL and CLL 

The first-ever CAR T-cell therapy was approved in 2017 for the treatment of ALL in children and young adults up to age 25.  

In 2024, two more CAR T-cell therapies were approved for leukemias: one for adults with relapsed/refractory B-cell precursor ALL; the other for relapsed/refractory chronic lymphocytic leukemia after two previous therapies. 

While CAR T-cell therapies have been tested in acute myeloid leukemia (AML), none have been approved. Dana-Farber investigator Rizwan Romee, MD, is investigating the possibility of treatment AML with a different type of immunotherapy called natural killer (NK) cell therapy, in which immune cells called NK cells are engineered to fight cancer.  

Immunotherapy for a rare blood cancer 

Dana-Farber’s Andrew Lane, MD, PhD, uncovered details about the biology of a rare and highly aggressive blood cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). The work led to the discovery and later approval in 2018 of tagraxofusp, an immunotoxin that targets CD123, a receptor on the cancer cells. 

Lane and others are now testing this medicine in combination with other therapies in AML, a precursor of AML called myelodysplastic syndrome, and BPDCN.  

Learn more about Dana-Farber clinical trials for leukemia.