ASH24: Arcellx, Gilead report no CAR-T neurotoxicity in MM, but note three patient deaths

Arcellx and Gilead Sciences have presented promising data from a pivotal study regarding their BCMA-directed CAR-T cell therapy, anitocabtagene autoleucel (anito-cel). This therapy aims to stand out from existing treatments on the market by demonstrating a high response rate without neurotoxic side effects. However, the study also reported three patient deaths. The Phase II iMMagine-1 trial involved patients with fourth-line or higher relapsed or remitting multiple myeloma (MM).

Currently, the two BCMA-targeted CAR-T therapies approved for MM are Johnson & Johnson's Carvykti (ciltacabtagene autoleucel) and Bristol Myers Squibb's Abecma (idecabtagene vicleucel). Both treatments carry boxed warnings due to potential neurologic toxicities, such as immune effector cell-associated neurotoxicity (ICANS) and parkinsonism. In contrast, Arcellx and Gilead highlighted that anito-cel did not show signs of neurotoxic side effects observed in other treatments. Additionally, they emphasized their quicker manufacturing process for anito-cel, although specific production rates were not provided in the recent release. Comprehensive data is expected to be unveiled in December at the American Society of Hematology (ASH) meeting.

As per the data shared, by June 1, 58 patients had received anito-cel, with a minimum follow-up of two months and a median follow-up duration of 10.3 months. The therapy achieved a noteworthy overall response rate (ORR) of 95% and a complete response (CR) rate of 62%. Among the 39 patients evaluated for minimal residual disease testing, 92% were found to be negative. Comparing earlier data from Phase I, presented at last year's ASH meeting, anito-cel demonstrated a 100% ORR and 76% CR in 38 patients with a median follow-up of 26.5 months, indicating its competitive potential alongside Carvykti.

Although the median progression-free survival (PFS) and overall survival (OS) have not yet been reached in the iMMagine-1 study, initial results showed six-month PFS and OS rates of 90% and 95%, respectively. This suggests a strong efficacy profile for anito-cel in treating MM.

Regarding safety, the most common Grade ≥3 treatment-emergent adverse events (AEs) were cytopenias. Importantly, no patients experienced delayed neurotoxicities such as parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome. Any-grade ICANs were observed in 9% of the patients, while any-grade cytokine release syndrome (CRS) occurred in 84%. The majority of patients (79%) experienced either no or only Grade 1 CRS, underscoring the manageable safety profile of anito-cel. Nevertheless, there were three reported patient deaths in the study due to retroperitoneal hemorrhage, CRS, and fungal infection, with some adverse events being linked to anito-cel.

The data presented by Arcellx and Gilead reflect significant progress in the development of anito-cel as a viable CAR-T cell therapy for multiple myeloma. The upcoming ASH meeting is expected to provide further insights and updates on the iMMagine-1 study, potentially solidifying anito-cel's place in the MM treatment landscape.