Dr Nadeem on Efficacy and Safety of Arlo-Cel for R/R Myeloma

“The infusion was, overall, pretty well-tolerated. Patients experienced cytokine release syndrome [at a rate of] 84%, but nobody had grade three or greater CRS, so that was reassuring.”

Omar Nadeem, MD, medical oncologist at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, discussed updated efficacy and safety data for the GPRC5D-targeted CAR T-cell therapy arlocabtagene autoleucel (arlo-cel; BMS-986393) for the treatment of patients with relapsed/refractory multiple myeloma. During the 22nd Annual International Myeloma Society Meeting and Exposition, investigators presented findings from the phase 1 trial (NCT04656817), which examined arlo-cel in patients who had received 1 to 3 prior lines of therapy. The efficacy-evaluable population included 24 patients, with a median follow-up of 18.3 months (range, 3.8-24.3).

Findings revealed that arlo-cel induced an overall response rate (ORR) of 94%, including a complete response (CR) rate of 71%. Median time to response was 0.99 months (range, 0.9-2.9), and responses deepened over time, Nadeem noted. Minimal residual disease (MRD) negativity was achieved in 56.3% of evaluable patients (n = 16) at 10-5 sensitivity, with all negative patients achieving an MRD-negativite CR, he added. Median progression-free survival (PFS) was 24.3 months (95% CI, 12.5-not reached).

Regarding safety, Nadeem explained that cytokine release syndrome (CRS) occurred in 84% of patients; however, no grade 3 or more CRS effects were reported, and all cases were manageable. Hematologic toxicities were frequent, with neutropenia observed in approximately 80% of patients. All cytopenias resolved with supportive care. Infections occurred in 55% of patients, but no grade 3 or higher infections were reported. On-target, off-tumor toxicities included dysgeusia, nail changes, and skin effects, which were transient and observed in about one-third of patients. Two patients experienced neurotoxicity in the form of ataxia and gait disturbance, both of which were grade 2 and ongoing at the time of data cutoff. Importantly, no cases of immune effector cell–associated neurotoxicity syndrome (ICANS) or treatment-related deaths were observed.

Nadeem concluded that arlo-cel demonstrated high and durable response rates with a favorable safety profile in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy. He noted that a phase 3 trial (NCT0615479) is ongoing to compare arlo-cel with standard-of-care regimens in this setting.