Advances in Hematologic Malignancies
Issue 10, Spring 2019
— Nikhil Munshi, MD
Despite major advances in multiple myeloma therapy, with 10 new drugs available in the last decade and significant improvement in survival, patients still relapse, requiring novel therapeutic approaches. Recent improvement
in our understanding of immunology has allowed us to develop new immunotherapeutic approaches, which are effective in a number of cancers, including multiple myeloma.
The most recent innovative immunologic approach has been chimeric antigen receptor modified T (CAR T) cells, which have demonstrated ability to selectively kill cancer cells and also overcome all conventional drug-related resistance mechanisms. CAR T
cells are genetically-modified immune cells (T lymphocytes or natural killer cells) that specifically target antigens on multiple myeloma cells, resulting in killing of the tumor cells at the same time expansion of the cytotoxic CAR T cells.
In multiple myeloma, CAR T cells targeting B cell maturation antigen (BCMA) have been investigated in a number of studies and have demonstrated important disease-remitting activity. In trials of patients who have relapsed after at least 3 lines of therapy
including a proteasome inhibitor, immunomodulator and CD38-targeting antibody, the observed response rate exceeded 85 percent. Some enrolled patients who responded to BCMA-directed CAR T cells had as many as 8 prior therapeutic regimens. The responses
are deep with substantial fraction of patients achieving minimal residual disease (MRD)-negative status.
One of the challenges of CAR T-cell therapy is the specific adverse event profile, including cytokine release syndrome and neurotoxicity. In myeloma, such adverse effects are relatively milder and less frequent than observed in other blood cancers. Various
methods are being developed now to prevent or mitigate such adverse effects and to improve the response rates and outcomes.
We are also focused on making the existing BCMA CAR T cells more widely available, as well as combining CAR T cells with other agents early on in the disease course. My laboratory is examining mechanisms of resistance of myeloma relapses following CAR
T-cell therapy, in order to rationally develop the next generation of therapies that allows long-term survival and potential cure. At Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC), we are actively involved in this advanced investigation and are excited about the ability to control
the disease in very advanced stages where therapeutic options are limited.
Learn more about CAR T-Cell Therapy
Learn more about Dana-Farber's Multiple Myeloma Program