Arlo-Cel Shows Promise in Early-Line Relapsed Multiple Myeloma

Susan Bal, MD, associate professor at the University of Alabama in Birmingham, discusses the final results from an early-phase cohort evaluating arlocabtagene autoleucel (arlo-cel) for the treatment of relapsed or refractory multiple myeloma she presented at the European Hematology Association Congress.

Arlo-cel is a first-in-class chimeric antigen receptor (CAR) T-cell therapy that hits a novel, clinically validated target known as GPRC5D. Although the approved bispecific antibody talquetamab (Talvey) targets this same antigen, arlo-cel provides a cellular therapy option utilizing the same mechanism. Previous results had shown favorable outcomes in the late-relapsed setting; this analyzed cohort included approximately 31 patients who had received 1 to 3 prior lines of therapy.

The final safety data for this patient population is highly encouraging, showing no new or unexpected safety events. Notably, the cohort experienced zero high-grade cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Furthermore, there were no high-grade infections or severe on-target, off-tumor toxicities reported. Neurotoxicities of special interest with this therapy, such as ataxia, dysmetria, and gait disturbances, manifested in only 2 patients, both presenting as low-grade cases. Although hematologic toxicities were relatively common, they proved manageable and completely resolved across all affected patients within a median of 63 days.

In addition to its favorable safety profile, arlo-cel demonstrated profound clinical efficacy in this aggressive disease setting. The overall objective response rate reached a high of 91%, with an impressive 71% of patients achieving a complete response or better. Long-term survival metrics further emphasize this durability, showcasing an 18-month progression-free survival rate of 63% and an outstanding 18-month overall survival rate of 100%.

Looking ahead, investigators are leveraging minimal residual disease (MRD) as a coprimary end point in the upcoming QUINTESSENTIAL-2 trial (NCT06615479). By utilizing MRD negativity as a surrogate marker for long-term patient outcomes, researchers hope to achieve an accelerated readout of clinical trials. This strategy aims to secure faster regulatory pathways and ultimately deliver this effective GPRC5D-targeted cellular option to patients with multiple myeloma earlier in their disease course.