Updated findings from the phase II iMMagine-1 study show that anitocabtagene autoleucel (anito-cel), an investigational CAR T-cell therapy for relapsed or refractory multiple myeloma, continues to deliver high response rates with a reassuring safety profile. Researchers from The University of Texas MD Anderson Cancer Center reported that in a cohort of 117 heavily pretreated patients, anito-cel achieved an overall response rate of 97% and a complete response rate of 68%, with sustained progression-free and overall survival benefits at 12 and 18 months. The new data were presented by Krina Patel, MD at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 256).
Background
Anito-cel differs from currently approved B-cell maturation antigen (BCMA)–directed CAR T-cell therapies in that a fully synthetic protein is used, rather than an antibody-derived fragment, to recognize B-cell maturation antigen on multiple myeloma cells. This design is smaller and simpler, allowing for more efficient engineering and potentially facilitating more reliable manufacturing. Researchers anticipate that this streamlined receptor structure may also reduce the neurologic and gastrointestinal toxicities sometimes seen with other BCMA-targeted products.
Study Details
Trial participants were age ≥ 18 years and had experienced disease progression after a median of 3 prior lines of therapy (range = 3–8). Patients received lymphodepletion chemotherapy and an infusion of anito-cel at a target dose of 115 × 106 CAR T cells. The primary endpoint was overall response rate as assessed by independent review.
With extended follow-up, progression-free survival was 79% at 12 months and 66% at 18 months, while overall survival rates were 95% and 90%, respectively. At the time of data cutoff (May 2025), median progression-free survival and overall survival had not been reached.
Investigators observed no delayed or atypical neurologic toxicities, and most adverse events were transient and manageable. Grade ≥ 3 cytopenias were observed in a majority of patients (66% neutropenia, 24% anemia, and 24% thrombocytopenia), and most participants experienced low-grade cytokine-release syndrome that resolved quickly (only one severe case was reported). In addition, nine patients experienced neurotoxicity, nearly all grade 1 or 2. According to Dr. Patel, “These data are really encouraging for these patients because not only does anito-cel look to be highly effective, but the safety profile is very promising compared to the other therapies currently approved in this setting.” She noted that the durability of response “continues to look strong, even in this heavily pretreated population.”
Future Directions
A phase III study is already underway to evaluate anito-cel against current standard-of-care regimens in relapsed or refractory multiple myeloma. According to the authors, this process could result in a CAR T-cell therapy that is not only easier to produce, but has fewer neurologic or gastrointestinal side effects compared with other CAR T-cell therapy options.
Disclosure: The trial was supported by Arcellx. For full disclosures of all study authors, visit hematology.org.
