Arlo-Cel Meets ORR End Point in BCMA-Pretreated, Quadruple-Class Exposed R/R Myeloma

Arlocabtagene autoleucel (arlo-cel; BMS-986393), a potential first-in-class autologous GPRC5D-directed CAR T-cell therapy, generated a statistically significant and clinically meaningful overall response rate (ORR) in adult patients with quadruple-class exposed relapsed/refractory multiple myeloma who had received 4 or more prior lines of therapy, meeting the primary end point of the registrational phase 2 QUINTESSENTIAL trial (NCT06297226).¹

The study also met the key secondary end point of complete response (CR) rate in quadruple-class exposed patients after 4 or more prior lines of therapy, as well as the key secondary end points of ORR and CR rate in quadruple-class exposed patients who had received 3 or more prior lines of therapy, according to a news release from Bristol Myers Squibb.

Quadruple-class exposure was defined as prior treatment with an immunomodulatory inhibitor (IMiD), a proteasome inhibitor (PI), an anti-CD38 therapy, and a BCMA-targeted therapy. The company noted that QUINTESSENTIAL is the first pivotal trial to evaluate a therapy in quadruple-class exposed relapsed/refractory multiple myeloma following treatment with a prior BCMA-targeted therapy.

Safety data showed that the profile of arlo-cel was consistent with that of other CAR T-cell therapies and other GPRC5D-targeting therapies in multiple myeloma.

Results from QUINTESSENTIAL will be presented at an upcoming medical meeting.

“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,” Lynelle B. Hoch, president, Cell Therapy Organization, Bristol Myers Squibb, stated in a news release. “These topline results support arlo-cel's potential benefit for patients while showing a safety profile consistent with expectations. They underscore our continued innovation in multiple myeloma and highlight the value of targeting alternative proteins, like GPRC5D, with the power of cell therapy to transform outcomes, laying the foundation for arlo-cel to become an important treatment option for this emerging group of patients who have been exposed to prior BCMA-targeted therapies.”

How was QUINTESSENTIAL designed?

QUINTESSENTIAL is a phase 2, open-label, multicenter, single-arm study evaluating the efficacy and safety of arlo-cel in adult patients with quadruple-class exposed relapsed/refractory multiple myeloma.²

To be eligible, patients needed a documented diagnosis of multiple myeloma per International Myeloma Working Group (IMWG) criteria; prior treatment with at least 4 classes of therapy, including an IMiD, a PI, an anti-CD38 monoclonal antibody, and an anti-BCMA therapy, plus at least 3 prior lines of therapy; documented disease progression during or after their last antimyeloma regimen; measurable disease at screening; and an ECOG performance status of 0 or 1. The trial permitted patients who had received prior CAR T-cell therapy but excluded those who had received any prior GPRC5D-directed treatment.²

Arlo-cel was administered as a single infusion following lymphodepleting chemotherapy.

The primary end point is ORR, defined as a best overall response of partial response or better, in quadruple-class exposed patients who received 4 or more prior lines of therapy; key secondary end points include CR rate, ORR and CRR after 3 or more prior lines, minimal residual disease negativity, duration of response, progression-free survival, and overall survival.

References

1. 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. News release. Bristol Myers Squibb. September 8, 2026. Accessed September 8, 2026. https://news.bms.com/news/corporate-financial/2026/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----/default.aspx
2. A phase 2, open-label, multicenter study of arlocabtagene autoleucel (BMS-986393), a GPRC5D-directed CAR T cell therapy in adult participants with relapsed or refractory multiple myeloma (QUINTESSENTIAL). ClinicalTrials.gov. Updated May 28, 2026. Accessed September 8, 2026. https://clinicaltrials.gov/study/NCT06297226