A phase 1 clinical trial led by investigators at Mass General Brigham Cancer Institute and the University of Chicago Medicine Comprehensive Cancer Center has found that an investigational CAR-T therapy can lead to deep and durable responses in people with relapsed/refractory multiple myeloma. Results are published in The New England Journal of Medicine .
Patients with relapsed or refractory multiple myeloma often run out of effective treatment options after multiple rounds of therapy. Contributing to this challenge is the fact that some existing CAR-T cell therapies targeting BCMA, a protein expressed on the surface of myeloma cells, have been linked to rare but serious neurological side effects.
The research team reported the results from a Phase 1 clinical trial of anitocabtagene autoleucel (anito-cel), an investigational BCMA-targeted CAR-T cell therapy that is being developed by Kite, a Gilead company.
All 38 treated participants responded to the therapy, and nearly 80% achieved a complete response. Many experienced long-lasting benefits, with more than half remaining progression-free two years later and 65% still alive after three years. Serious immune-related and neurological side effects were uncommon, and no delayed neurological complications were reported.
“These were great results for a Phase 1 trial,” said senior author Michael R. Bishop, MD, Professor of Medicine and Director of the David and Etta Jonas Center for Cellular Therapy at UChicago Medicine. “Even at a low dose of anito-cel, we were seeing complete responses in the majority of patients right off the bat, and not a single patient developed severe toxicities, so we wanted to investigate further why that might be.”
Based on their laboratory analyses, the researchers hypothesized that anito-cel's engineered BCMA-binding domain maintained cancer-killing activity while limiting excessive immune activation and other features that can impair CAR-T cell function or contribute to toxicity.
“The absence of neurotoxic and inflammatory side effects in this phase 1 study is particularly encouraging, given the serious and potentially lasting impact of these complications,” said lead author Matthew Frigault, MD, vice chair of Clinical Research in Hematology/Oncology and deputy program director of the Cellular Immunotherapy Program at the Mass General Brigham Cancer Institute. “The novel D-domain binder may contribute to this finding, and the combination of compelling efficacy and encouraging safety data lay important groundwork for continuing to investigate this new treatment option for patients."
Anito-cel is currently being evaluated in Phase 2 and Phase 3 clinical trials to confirm these findings in larger populations of patients with multiple myeloma.
Authorship: In addition to Frigault and Bishop, authors include Binod Dhakal, Andrzej J. Jakubowiak, Noopur Raje, Kamalika Banerjee, C. Jenny Mu, Kevin C. Hart, Sigal Shachar, Lawrence P. Andrews, Laurene S. Cheung, Faith M. Griffin, Alexandra R. Witter, Michael Hyde, Chester Pham, Nikitha Gandra, Tenzin Shakya, Bhargavi Rajan, Christa Cortesio, Samuel T. Haile, Heba Nowyhed, Priyanka Nair-Gupta, Priyam Mitra, Rebecca J. Chan, Ana Kostic, Christopher R. Heery, and Jacalyn Rosenblatt.
Paper cited: Frigault MJ et al. “Anito-cel, a D-Domain BCMA CAR-T: Phase 1 Results and Binder Characterization” NEJM DOI: 10.1056/NEJMoa2603527
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About UChicago Medicine
The University of Chicago Medicine Comprehensive Cancer Center has been at the forefront of cancer care and discovery for more than 50 years. Many of the roots of chemotherapy, hormonal therapy, gene therapy and bone marrow transplantation can be traced back to the University of Chicago. More than 200 physician scientists are conducting basic, clinical and translational research to study cancer from all angles, enabling the incorporation of personalized medicine into routine care. The Cancer Center is one of only 58 National Cancer Institute-designated Comprehensive Cancer Centers , a distinction that denotes scientific excellence, as well as discovery and development of effective approaches to cancer risk assessment, prevention, diagnosis, treatment, and survivorship.
New England Journal of Medicine
Randomized controlled/clinical trial
People
Anito-cel, a D-Domain BCMA CAR-T: Phase 1 Results and Binder Characterization
23-Sep-2026
A full list of author disclosures can be found in the published paper.