Bristol Myers Squibb's GPRC5D-Directed CAR T Cell Therapy Meets Primary Endpoint in Multiple Myeloma

Bristol Myers Squibb announced positive topline results from the registrational Phase 2 QUINTESSENTIAL trial (NCT06297226) of arlocabtagene autoleucel (arlo-cel; BMS-986393), a potential first-in-class autologous CAR T cell therapy directed against G protein-coupled receptor class C group 5 member D (GPRC5D), in adults with quadruple-class exposed relapsed and refractory multiple myeloma (RRMM).¹ The trial met its primary endpoint of overall response rate (ORR) in patients who had received four or more prior lines of therapy, including an immunomodulatory inhibitor, a proteasome inhibitor, an anti-CD38 therapy, and a BCMA-targeted therapy.¹ The trial also met the key secondary endpoint of complete response rate in that same quadruple-class exposed population, as well as key secondary endpoints of ORR and complete response rate in patients who had received three or more prior lines of therapy.¹ The safety profile of arlo-cel was consistent with that of other CAR T cell therapies and other GPRC5D-targeting therapies in multiple myeloma.¹ Full results will be presented at an upcoming medical meeting.¹

What is the significance of this trial's patient population?

QUINTESSENTIAL is the first pivotal trial to evaluate a therapy specifically in quadruple-class exposed RRMM patients who have already been treated with a prior BCMA-targeted therapy — a population with an especially high unmet need, since most currently available myeloma therapies target BCMA, leaving few options once that target has been exhausted.¹ GPRC5D expression on myeloma cells is independent of BCMA expression and is maintained even after prior BCMA-directed therapy, which is the biological rationale for pursuing it as an alternate target in this specific patient population.¹

Lynelle B. Hoch, president, Cell Therapy Organization, Bristol Myers Squibb, said, "As combination treatment regimens are now frequently used in earlier lines of therapy, an increasing number of people with multiple myeloma are quadruple-class exposed and resistant to currently available therapies earlier in the treatment journey, creating a critical need for new therapeutic approaches. These topline results support arlo-cel's potential benefit for patients while showing a safety profile consistent with expectations."¹

How does GPRC5D compare with other myeloma targets, and who else is pursuing it?

GPRC5D is a receptor expressed on plasma cells in multiple myeloma with limited expression on healthy cells, a profile that has made it an increasingly validated therapeutic target across several modalities.² Johnson & Johnson's talquetamab, a GPRC5D-targeting bispecific antibody, received initial FDA approval in 2023 and has since been used in more than 11,000 patients, and Johnson & Johnson has continued expanding its GPRC5D and BCMA combination strategies, including its Tecvayli-Talvey combination, which cut progression risk 89% in earlier-line RRMM. Innovent Biologics has also advanced a GPRC5D/BCMA/CD3 trispecific antibody, IBI3003, into phase 3, reflecting a broader industry push to engage myeloma cells across multiple targets simultaneously. Arlo-cel represents a distinct approach within that same competitive landscape — a CAR T cell therapy rather than a bispecific or trispecific antibody, designed as a single infusion following T-cell collection, bridging therapy, manufacturing, and lymphodepleting chemotherapy.¹

Manufacturing strategy remains a defining challenge across advanced cell therapies broadly. Miguel Forte, MD, PhD, chief executive officer of Kiji Therapeutics and president of the International Society for Cell and Gene Therapy, told BioPharm International in a video interview at the 2025 Cell and Gene Meeting on the Mesa that developers should resist "reinventing the wheel" in favor of proven approaches: "We are adopting solutions and approaches that people are comfortable with. We don't have to reinvent the wheel. We have to use the wheel appropriately for our engine, for our vehicle."³ Bristol Myers Squibb said it is currently the only company with two approved CAR T cell therapies with two distinct targets available in major markets, referring to its existing BCMA-directed and CD19-directed products.¹

What happens next?

Full QUINTESSENTIAL results will be presented at an upcoming medical meeting.¹ Arlo-cel is also being evaluated in earlier-phase combination studies pairing it with other myeloma therapies, including alnuctamab, mezigdomide, and iberdomide.⁴ Bristol Myers Squibb has not disclosed a regulatory filing timeline based on these topline results.

References

1. Bristol Myers Squibb. Bristol Myers Squibb Announces Positive Topline Results from Registrational Phase 2 QUINTESSENTIAL Trial of the Potential First-in-Class GPRC5D-Directed CAR T Cell Therapy, Arlocabtagene Autoleucel, in Patients with Quadruple-Class Exposed Relapsed and Refractory Multiple Myeloma. Press release. Published September 8, 2026. Accessed September 8, 2026.
2. Rodriguez-Otero P, van de Donk NWCJ, Pillarisetti K, et al. GPRC5D as a Novel Target for the Treatment of Multiple Myeloma: A Narrative Review. Blood Cancer J. 2024;14(1):24. doi:10.1038/s41408-023-00966-9.
3. Mirasol F. Why Product-Specific Strategies Matter in Advanced Therapy Manufacturing (Part 3). BioPharm International. Published October 16, 2025. Accessed September 8, 2026.
4. ClinicalTrials.gov. A Study to Evaluate the Safety, Effectiveness and Tolerable Dose of Arlocabtagene Autoleucel (BMS-986393) in Novel Combinations in Participants With Relapsed and/or Refractory Multiple Myeloma. NCT06121843. Accessed September 8, 2026.