Bristol Myers Squibb has announced positive topline results from the registrational Phase 2 QUINTESSENTIAL trial, evaluating arlocabtagene autoleucel (arlo-cel; BMS-986393) in patients with heavily pretreated relapsed or refractory multiple myeloma.
The study met its primary endpoint of overall response rate (ORR) as well as key secondary endpoints, including complete response rate (CRR), in patients with quadruple-class exposed relapsed or refractory multiple myeloma who had previously received BCMA-targeted therapy.
The company announced the results on September 8, 2026. Detailed response rates and other efficacy data were not disclosed in the topline announcement and are expected to be presented at an upcoming medical meeting.
QUINTESSENTIAL Trial Meets Primary and Secondary Endpoints
QUINTESSENTIAL (NCT06297226) is a Phase 2, open-label, multicenter, single-arm study assessing the efficacy and safety of arlocabtagene autoleucel in adults with relapsed or refractory multiple myeloma.
The primary endpoint was ORR, defined as a best overall response of partial response or better, among quadruple-class exposed patients who had received at least four prior lines of therapy.
According to Bristol Myers Squibb, arlocabtagene autoleucel produced a statistically significant and clinically meaningful ORR in this population. The trial also met its key secondary endpoint of CRR.
Additional key secondary endpoints of ORR and CRR among quadruple-class exposed patients who had received at least three previous lines of therapy were also met.
Quadruple-class exposure was defined as previous treatment with:
- an immunomodulatory drug,
- a proteasome inhibitor,
- an anti-CD38 therapy, and
- a BCMA-targeted therapy.
The study also permitted enrollment of patients who had previously received CAR T-cell therapy.
Safety of Arlocabtagene Autoleucel
Bristol Myers Squibb reported that the safety profile of arlocabtagene autoleucel was consistent with the known safety profiles of other CAR T-cell therapies and GPRC5D-targeting treatments used in multiple myeloma.
Specific rates of cytokine release syndrome, neurotoxicity, cytopenias and other adverse events were not provided in the topline announcement.
Lynelle B. Hoch, President of the Cell Therapy Organization at Bristol Myers Squibb, highlighted the growing treatment need among patients who become resistant to several therapeutic classes:
“An increasing number of people with multiple myeloma are quadruple-class exposed and resistant to currently available therapies.”
She added that the results support the potential of targeting alternative proteins such as GPRC5D in patients previously exposed to BCMA-directed therapies.
What Is Arlocabtagene Autoleucel?
Arlocabtagene autoleucel is an investigational autologous GPRC5D-directed chimeric antigen receptor (CAR) T-cell therapy being developed for multiple myeloma.
GPRC5D, or G protein-coupled receptor class C group 5 member D, is expressed on plasma cells in multiple myeloma while having more limited expression in healthy tissues.
Importantly, GPRC5D expression is independent of B-cell maturation antigen (BCMA) expression and may remain present following previous BCMA-directed treatment. This makes GPRC5D an alternative therapeutic target for patients whose disease has progressed following BCMA-targeted approaches.
Arlocabtagene autoleucel is designed to recognize GPRC5D and direct the patient’s genetically modified T cells against GPRC5D-expressing myeloma cells.
The treatment is administered as a single CAR T-cell infusion following T-cell collection, manufacturing, bridging therapy when required, and lymphodepleting chemotherapy.
Earlier Phase 1 findings supported further development of the therapy in heavily pretreated relapsed or refractory multiple myeloma, including patients previously treated with BCMA-directed therapies.
Next Steps for Arlocabtagene Autoleucel
The QUINTESSENTIAL trial is intended to support the development of arlocabtagene autoleucel in heavily pretreated multiple myeloma.
Bristol Myers Squibb stated that complete results from the study will be presented at an upcoming medical meeting. The company has not yet reported the numerical ORR or CRR, duration of response, progression-free survival or detailed safety findings from the registrational Phase 2 study.
Arlocabtagene autoleucel is also being investigated as part of the broader clinical development program exploring GPRC5D-directed CAR T-cell therapy across earlier settings of relapsed or refractory multiple myeloma.
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