Dr Hansen on the Potential Role of GPRC5D-Targeted CAR T-Cell Therapy in Myeloma

What I like about the GPRC5D-targeting CAR T[-cell therapy] is that it provides us with a unique and different target [for] patients who have a significant unmet need.

Doris Hansen, MD, an associate member in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, discussed emerging data for GPRC5D-directed CAR T-cell therapy in multiple myeloma, and how a target beyond BCMA could address a growing population of patients with heavily pretreated disease. During a presentation at Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma, Hansen explored the potential utility of a CAR T-cell therapy with a novel target such as GPRC5D and discussed data for arlocabtagene autoleucel (arlo-cel; BMS-986393), which has displayed positive efficacy and safety data in clinical studies.

Immunotherapies are driving a revolution in multiple myeloma, and CAR T-cell therapies directed at a range of targets are among the most exciting developments, Hansen said. She highlighted data from a first-in-human phase 1 study (NCT04674813), which were presented at the 2024 ASH Annual Meeting and Exposition. In the study, arlo-cel yielded an overall response rate (ORR) of 87% among efficacy-evaluable patients (n = 79), with a complete response (CR) rate of 53% and a median progression-free survival of 18.3 months (95% CI, 11.8-21.9).

Hansen also pointed to the positive topline results from the phase 2 registrational QUINTESSENTIAL trial (NCT06297226), which met its primary end point of ORR in patients with quadruple-class–exposed relapsed/refractory multiple myeloma who had received at least 4 prior lines of therapy, as well as key secondary end points including CR rate.

According to Hansen, the value of a GPRC5D-directed approach lies in the shifting treatment landscape. Since patients now receive quadruplet regimens in the frontline setting, they are becoming triple-class exposed and triple-class refractory earlier in their disease course, she explained. As BCMA-directed agents move into earlier relapsed/refractory lines, a growing number of patients will also become quadruple-class exposed and refractory, making new targets essential, Hansen added.

She noted that defining cure in multiple myeloma was a major focus of discussion at the 23rd International Myeloma Society Annual Meeting in September 2026, and that novel immunotherapies have brought the field closer to that goal. GPRC5D-directed CAR T-cell therapy is poised to further contribute in that space as the search for a definitive cure continues, Hansen concluded.