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BMS’s GPRC5D CAR-T clears registrational trial in quadruple-exposed multiple myeloma

BMS’s GPRC5D CAR-T clears registrational trial in quadruple-exposed multiple myeloma

Arlocabtagene autoleucel met the primary endpoint of overall response rate (ORR) and all key secondary endpoints in the registrational QUINTESSENTIAL Phase II trial, Bristol Myers Squibb (NYSE: BMY) reported on September 8, 2026. The result positions the GPRC5D-directed CAR T cell therapy for a BLA submission targeting one of the most treatment-resistant populations in multiple myeloma: patients who have already progressed through an immunomodulatory drug, a proteasome inhibitor, an anti-CD38 antibody, and a BCMA-directed therapy.

The trial enrolled adults with quadruple-class exposed relapsed or refractory multiple myeloma (RRMM) who had received at least four prior lines of therapy. BMS described the ORR improvement as statistically significant and clinically meaningful; the complete response rate (CRR) secondary endpoint was also met, as were ORR and CRR endpoints in a broader cohort with three or more prior lines. No numerical data were disclosed — full results are expected at an upcoming medical conference. The safety profile was described as consistent with other CAR T and GPRC5D-targeting therapies.

Arlo-cel, as it is also known, targets GPRC5D, a receptor expressed on malignant plasma cells whose expression is independent of BCMA and is maintained after prior BCMA-directed therapy. By directing engineered autologous T cells against a non-BCMA antigen, the therapy is designed to retain activity in patients where BCMA-targeted agents have already failed. Phase I data presented at ASH 2024 showed an ORR of 87% at a median follow-up of 16.1 months, with median progression-free survival of 18.3 months and median overall survival not reached.

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Currently Johnson & Johnson's Talvey (talquetamab-tgvs), a GPRC5D×CD3 bispecific antibody, is the only currently approved GPRC5D-targeted therapy and offers a non-BCMA option that can be used after prior BCMA-directed treatment. Talquetamab requires ongoing subcutaneous dosing on a weekly or biweekly schedule. Arlo-cel, as a CAR T therapy, is designed as a single infusion — a structural differentiator that, if efficacy and safety hold at scale, could alter prescribing patterns in this setting. Approved BCMA-directed CAR T therapies — BMS's own Abecma (idecabtagene vicleucel) and Johnson & Johnson's Carvykti (ciltacabtagene autoleucel) — generally show lower response rates or shorter durability after prior BCMA exposure, increasing interest in alternative targets such as GPRC5D, and BCMA bispecifics elranatamab and teclistamab show reduced efficacy in BCMA-pre-exposed patients.

BMS said QUINTESSENTIAL is the first pivotal trial to evaluate a therapy specifically in quadruple-class exposed RRMM following prior BCMA-targeted therapy. The company has the QUINTESSENTIAL-2 Phase III randomized study already recruiting, comparing arlo-cel against standard of care in lenalidomide-refractory RRMM — a broader population that would support a larger commercial label if approved. BMS said detailed QUINTESSENTIAL results will be presented at an upcoming medical meeting, with the detailed results expected to inform a potential BLA submission..


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