Arlo-Cel Meets Efficacy End Point in Quadruple-Class Exposed Myeloma

A trial of arlocabtagene autoleucel (arlo-cel; BMS-986393), a GPRC5D-directed chimeric antigen receptor (CAR) T-cell therapy, met its primary end point of overall response rate (ORR) in adult patients with quadruple-class exposed relapsed/refractory multiple myeloma (RRMM), according to topline results.¹

The QUINTESSENTIAL trial (NCT06297226) demonstrated a statistically significant and clinically meaningful ORR among patients with quadruple-class exposed disease who had received 4 or more prior lines of therapy. The trial also met the key secondary end point of complete response rate (CRR) in this population, as well as key secondary end points of ORR and CRR among quadruple-class–exposed patients who had received 3 or more prior lines of therapy.

QUINTESSENTIAL Trial Design

QUINTESSENTIAL is a phase 2, open-label, multicenter, single-arm trial evaluating the efficacy and safety of arlo-cel in patients with quadruple-class exposed RRMM, including patients who had previously received B-cell maturation antigen (BCMA) CAR T-cell therapy. The trial is the first pivotal study to evaluate a therapy in this quadruple-class exposed population following prior BCMA-targeted therapy.

Quadruple-class–exposed disease was defined as prior treatment with an immunomodulatory inhibitor, a proteasome inhibitor, an anti-CD38 therapy, and a BCMA-targeted therapy. Patients could not have received any other prior GPRC5D-targeted therapy. The safety profile of arlo-cel is consistent with that of other CAR T-cell and other GPRC5D-targeting therapies in multiple myeloma.

Promising Phase 1 Data for Arlo-Cel

Arlo-cel is a potential first-in-class autologous GPRC5D-directed CAR T-cell therapy. GPRC5D is expressed on plasma cells in multiple myeloma but has limited expression on healthy cells, and it is expressed even after prior BCMA-directed therapy. Arlo-cel is designed to bind to GPRC5D to destroy myeloma cells.

According to findings presented at the 2026 European Hematology Association Annual Congress, in a phase 1 trial (NCT04674813) of patients who had received 1 to 3 prior lines of therapy, arlo-cel resulted in a 94% ORR and CR or better rate of 71% among 31 evaluable patients, with an 18-month duration of response rate of 64.6%. Importantly, no grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome was reported.

“These topline results support arlo-cel’s potential benefit for patients while showing a safety profile consistent with expectations. Lynelle B. Hoch, president of the Cell Therapy Organization at Bristol Myers Squibb, stated in the news release. Full results from QUINTESSENTIAL are planned for presentation at an upcoming medical meeting.¹

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. Accessed September 8, 2026. https://tinyurl.com/3ehy9ad3

2. Bal S, Htut M, Berdeja J, et al. Arlocabtagene autoleucel, a GPRC5D-targeted CAR T-cell therapy for patients with relapsed/refractory multiple myeloma: updated phase 1 safety and efficacy results in patients with 1-3 prior regimens. Presented at: EHA2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S200.