Novel Immunotherapy Combinations in Relapsed, Refractory Mantle Cell Lymphoma
Anita Kumar
MDMemorial Sloan Kettering Cancer Center
Project Term: July 1, 2024 - June 30, 2029
We are evaluating two parallel clinical trials with synergistic immunotherapies in mantle cell lymphoma (MCL), including 1) tafasitamab and lenalidomide and 2) glofitamab and lenalidomide. We will investigate how these treatments impact the MCL immune microenvironment and mediate anti-tumor immune responses, and will correlate these changes with outcome.
Our goal is to develop safe, effective, and "off-the-shelf" immunotherapies to improve outcomes for patients with relapsed, refractory MCL.
Mantle cell lymphoma (MCL) is a rare form of B-cell non-Hodgkin lymphoma that is unfortunately incurable with current treatments. When the MCL relapses after initial chemotherapy, patients are typically treated with a targeted therapy called a Bruton’s Tyrosine Kinase (BTK) inhibitor. Once the BTK inhibitor stops working, however, there are limited treatment options available for relapsed MCL. One recent advance for the treatment of relapsed MCL was the development of a cellular immune therapy called chimeric antigen receptor T-cell (CAR-T) therapy. Despite the promising activity of CAR-T, not all MCL patients are able to receive this therapy. Some patients may not be eligible for CAR-T therapy due to advanced age or other medical conditions. In addition, CAR-T for MCL necessitates inpatient admission at a highly specialized center which can limit access. Finally, CAR-T requires advance planning and time for manufacturing which can represent challenges for patients who are in need of treatment right away.
Given this context, there is an urgent need to develop new, “off-the-shelf” immunotherapies to treat relapsed MCL. In the current research proposal, we are studying two novel outpatient immunotherapy combinations including an oral immunomodulatory drug called lenalidomide. In addition to its known anti-cancer activity in MCL, lenalidomide can activate immune cells to fight against cancer cells and enhance the activity of other immunotherapies. In the first phase 2 study, we are testing the efficacy of the combination of lenalidomide with tafasitamab, an antibody that binds to the CD19 protein and triggers a patient’s immune system to attack lymphoma cells. In the second pilot study, we are testing the feasibility, safety, and efficacy of the combination of lenalidomide and glofitamab, a bispecific antibody that targets CD20 on MCL cells and CD3 on a patient’s T-cells. In these two clinical trials, we will collect blood, lymph node, and bone marrow samples from patients at several timepoints before and after treatment in order to study the dynamic changes in immune cell populations that occur after immunotherapy, as well as characterize anti-lymphoma immune responses. Our research may not only expand outpatient immunotherapy treatment options for relapsed MCL patients, but it may also help us to better identify markers of response and resistance to immunotherapy in MCL and facilitate the development of more effective immunotherapy strategies for MCL.