Dr Leick on the Use of CAR T-Cell Therapy Across Hematologic Malignancies

Mark Leick, MD, physician investigator, CCR Group C Monthly, Massachusetts General Research Institute, assistant professor, medicine, Harvard Medical School, assistant in medicine, Medicine-Hematology/Oncology, Massachusetts General Hospital, discusses the varying role of CAR T-cell therapy across various hematologic malignancies, elaborating on the cause of its effectiveness in these disease spaces.

CAR T-cell therapies are designed to target tumor-specific antigens, Leick begins, stating that the most common target is CD19. This marker is found on B-cells and is expressed in a variety of lymphomas. The success of this drug class has been notable in B-cell malignancies including acute lymphoblastic leukemia and diffuse large B-cell lymphoma, leading to initial approvals in both disease types, Leick says.

Over time, the use of CAR T-cell therapy has expanded to other B-cell lymphomas such as mantle cell lymphoma or follicular lymphoma, the latter of which is considered less aggressive, Leick describes. Notably, there have been 2 FDA approvals for CAR T-cell therapy in relapsed/refractory multiple myeloma: idecabtagene vicleucel (Abecma) was approved in March, 2021, and ciltacabtagene autoleucel (Carvykti) was approved in February, 2022. Both are currently used for the treatment of patients whose disease has progressed on 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The key to this success lies in the fact that CD19 is expressed on normal B cells in the body, which are not essential for survival, Leick explains. Patients can therefore receive artificial replacements for the immunoglobulins produced by B cells, allowing them to function normally without these cells, he adds.

This targeted approach has enabled CAR T-cell therapy to address a wide spectrum of cancers associated with B cells while minimizing the impact on essential bodily functions, Leick states. Ultimately, these outcomes reflect the precision and adaptability of this treatment modality, he concludes.