Bristol Myers Squibb Sees Success With CAR T Therapy
Bristol Myers Squibb announced positive topline results from the phase 2 QUINTESSENTIAL clinical trial evaluating arlocabtagene autoleucel, an investigational CAR T-cell therapy for people with relapsed or refractory multiple myeloma who have already received several types of treatment. The trial met its primary endpoint of overall response rate (ORR), as well as its key secondary endpoint of complete response rate (CRR), in patients whose disease had been treated with four major classes of multiple myeloma therapies, including a prior BCMA-targeted treatment.
The QUINTESSENTIAL trial found that arlo-cel met its primary goal of overall response rate in patients with relapsed or refractory multiple myeloma who had received four or more previous lines of treatment, including a prior BCMA-targeted therapy. The trial also met its key secondary goal of complete response rate in this patient population. Additional key endpoints evaluating overall response rate and complete response rate in patients who had received at least three prior lines of treatment were also met.
For the trial, “quadruple-class exposed” refers to patients who had previously received an immunomodulatory drug, a proteasome inhibitor, an anti-CD38 therapy and a BCMA-targeted therapy. Bristol Myers Squibb described the overall response rate as statistically significant and clinically meaningful. The company has not yet released the specific response percentages from the QUINTESSENTIAL trial. More detailed results are expected to be presented at an upcoming medical meeting.
The company reported that the safety profile of arlo-cel was consistent with what has been observed with other CAR T-cell therapies and GPRC5D-targeting treatments in multiple myeloma. Specific rates of individual side effects were not included in the topline announcement.
A Different Target for Multiple Myeloma
Arlo-cel is designed to target GPRC5D, a protein found on plasma cells involved in multiple myeloma. This approach is different from BCMA-directed therapies, which target another protein commonly found on myeloma cells. GPRC5D expression is independent of BCMA expression and can remain present after treatment with a BCMA-directed therapy. This makes GPRC5D an area of interest for researchers looking for new treatment approaches for patients whose disease has progressed after BCMA-targeted treatment.
QUINTESSENTIAL is notable because it is evaluating a therapy in patients who have already received treatment targeting BCMA. According to Bristol Myers Squibb, it is the first key trial to evaluate a therapy in this particular quadruple-class exposed population following prior BCMA-targeted treatment. The therapy remains investigational and is not currently approved by the FDA for the treatment of multiple myeloma. Bristol Myers Squibb’s clinical trial information states that the therapy has not been evaluated by the FDA as safe or effective for multiple myeloma.
How Arlo-cel Works
Arlo-cel is an autologous CAR T-cell therapy, meaning it uses a patient’s own T cells. During the treatment process, T cells are collected from the patient’s blood and modified in a laboratory to recognize and attack cells carrying GPRC5D. The modified cells are then given back to the patient as a single infusion. Before the infusion, patients receive lymphodepleting chemotherapy to prepare the body for the CAR T cells.
Multiple myeloma is a blood cancer that can return or become resistant to treatment over time. As patients receive more lines of therapy, treatment options can become increasingly limited. The QUINTESSENTIAL results are particularly relevant to patients whose multiple myeloma has already been treated with several major classes of therapies, including a BCMA-targeted treatment. The findings also highlight the potential of targeting a different protein after a patient’s disease has progressed following BCMA-directed treatment.
More complete results from QUINTESSENTIAL are expected at an upcoming medical meeting and will help provide a clearer picture of the therapy’s effectiveness, duration of response and safety.
Understanding CAR T-Cell Therapy
CAR T-cell therapy is a type of personalized cancer treatment that uses a patient’s own immune cells. T cells are collected from the patient’s blood and modified so they can recognize a specific target on cancer cells. After the modified cells are manufactured, the patient receives chemotherapy to prepare the body for the CAR T-cell infusion. The modified T cells are then given back to the patient, where they can seek out and attack cells carrying the targeted protein.
CAR T-cell therapies can cause serious side effects, including cytokine release syndrome and neurological toxicities, which is why patients receiving these treatments require close monitoring. For people with relapsed or refractory multiple myeloma, researchers continue to investigate new targets and treatment strategies that could provide additional options when the disease progresses after existing therapies. ClinicalTrials.gov lists the study as NCT06297226.
