Posted: Monday, October 2, 2023
“Immunotherapy has changed the treatment paradigm for myeloma,” stated Shaji K. Kumar, MD, of the Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, at the recent 2023 NCCN Annual Congress: Hematologic Malignancies. However, he added, the ideal place in which to use these newer agents for maximal efficacy with minimal toxicity is not yet clear.
Dr. Kumar discussed the latest data on the four main categories of immunotherapies being used in the management of multiple myeloma: naked antibodies, which include the anti-CD38–targeted antibodies daratumumab and isatuximab and the SLAMF7-targeted antibody elotuzumab; bispecific T-cell engagers, which include two that target B-cell maturation antigen (BCMA), teclistamab-cqyv and elranatamab-bcmm, and one that targets GPR5D, talquetamab-tgvs; the antibody-drug conjugate belantamab mafodotin-blmf, which also targets BCMA; and chimeric antigen receptor (CAR) T-cell therapies such as idecabtagene vicleucel and ciltacabtagene autoleucel, both of which target BCMA.
“The two categories of treatments I think have revolutionized myeloma therapy and will continue to do so are the T-cell redirection therapies, which are incredibly effective,” Dr. Kumar said. T-cell redirection therapies are now being incorporated into the algorithm for the early-intervention phase through the relapsed or refractory disease stage.
“We have probably a dozen of these bispecific antibodies against different targets going through clinical trials. In almost all, we have seen response rates of 60% to 70%, suggesting their efficacy may not necessarily be that dependent on the antigen you’re targeting as much as the ability of T cells to actually counter the tumor cell,” he explained.
However, Dr. Kumar noted, there are many questions still to be answered. “For instance,” he posed, “if you’re incorporating monoclonal antibodies in the treatment of newly diagnosed myeloma, which patients need it, and where should you use it—induction, maintenance, both, neither? We still don’t know whether all patients need a four-drug combination and whether with four drugs, we can shorten the treatment duration. There’s a lot more to learn about the ideal combination for a given patient, based on clinical characteristics.”
Disclosure: Dr. Kumar reported financial relationships with AbbVie, Amgen, BeiGene, Bristol Myers Squibb, GSK, Janssen Pharmaceutical Products, Karyopharm Therapeutics, Loxo Oncology, Regeneron Pharmaceuticals, Roche Laboratories, Sanofi US, and Takeda Pharmaceuticals North America.