Anito-cel for Multiple Myeloma: What to Know

  • Anito‑cel’s synthetic d‑domain binder — engineered for fast antigen off‑rate — may deliver potent myeloma killing with less T‑cell overactivation, showing comparable cytotoxicity to existing BCMA CAR T constructs but markedly lower cytokine release in preclinical models.
  • In a high‑risk, heavily pretreated phase 1 population, anito‑cel produced near‑universal responses (100% ORR), deep remissions (79% CR+), durable benefit (median PFS 30.2 months), and high MRD‑negativity, with largely low‑grade CRS and minimal neurotoxicity.
  • Early data suggest CAR architecture, including antigen‑binding kinetics, may meaningfully shape the balance between efficacy and inflammation, though confirmation will require larger, randomized trials such as the ongoing phase 2 iMMagine‑1 study.

The BCMA CAR T-cell landscape in multiple myeloma continues to evolve, and the recently published phase 1 study of anitocabtagene autoleucel (anito-cel) introduces an intriguing approach to CAR design.

Unlike currently available BCMA-directed CAR T products, anito-cel uses a novel, synthetic d-domain BCMA-binder, a small, non-antibody engineered binder designed to have a relatively fast antigen off-rate. The proposed rationale is that transient antigen engagement may provide sufficient signaling for tumor killing while limiting excessive T-cell activation, cytokine release, and potentially prolonged inflammatory toxicity.

Preclinical work demonstrated a markedly faster off-rate than a cilta-cel type dual-VHH binder, with comparable myeloma cytotoxicity but substantially lower cytokine release.

“The recently published phase 1 NEJM study of anito-cel in 38 heavily pretreated patients showed impressive depth and durability of response with an encouraging safety profile,” Dr. Gurbakhash Kaur, a hematologist/oncologist at Mount Sinai, tells SurvivorNet Connect.

Dr. Kaur adds that the phase 2 iMMagine-1 data presented at ASH 2025 reinforces these findings in a larger cohort.

“If approved later this year, I believe anito-cel will become an important addition to our treatment armamentarium for patients with relapsed or refractory multiple myeloma,” she explains.

The Data: Anito-cel in Action

The phase 1 study enrolled 40 heavily pretreated patients with R/R MM, of whom 38 received anito-cel. This was a particularly high-risk population where all patients were triple-class refractory and 68% were penta-drug refractory.

At a median follow-up of 38.1 months:

  • All 38 treated patients responded, with 79% achieving a CR or better and 92% achieving a VGPR or better.
  • Median duration of response was 29.1 months, and median PFS was 30.2 months, with a 24-month PFS of 57%.
  • OS at 36 months was 65%.

Among the 28 patients evaluable for MRD, 79% were MRD-negative, and sustained MRD negativity appeared encouraging. These results are notable not simply because the response rate approaches 100%, but because responses appear deep and durable despite extensive prior therapy. Responses were also observed in patients with adverse clinical features such as EM disease and elevated B2M, although these subgroup analyses were small and descriptive.

CRS occurred frequently but was predominantly low grade.

At the recommended phase 2 dose, 94% developed grade 1-2 CRS, with no grade ≥3 CRS. ICANS occurred in 19% of patients at the recommended dose, 16% grade 1-2 and a single grade 3 event (3%); across all dose levels, the overall ICANS incidence was 18%.

No delayed or non-ICANS neurotoxicity was observed, and there were no cases of immune-mediated colitis. This is particularly relevant given the delayed neurologic and inflammatory toxicities reported with some BCMA CAR T products, including cilta-cel.

Three patients developed MDS during follow-up; investigators considered these events unrelated to anito-cel, and the events occurred after disease progression and subsequent therapy. This study cannot establish that the construct is responsible for the favorable safety profile, but the biologic story is compelling. 

Key Takeaways

The important takeaway is that CAR design may matter. BCMA CAR T therapies have largely been thought of as variations on the same therapeutic concept, same target with a different binding domain and manufacturing platform. The anito-cel data suggest that the kinetics and structure of the antigen-binding domain may meaningfully influence the balance between tumor killing and immune activation.

At the same time, these results should be interpreted as an important early signal rather than a definitive comparison with existing CAR T products. This was a small, single-arm phase 1 study, with no randomized or head-to-head comparison against ide-cel or cilta-cel. Cross-trial comparisons are therefore inherently limited. The population was also highly selected and predates widespread use of BCMA bispecific antibodies.

For now, anito-cel’s early clinical results provide proof of concept that engineering the CAR itself may preserve the depth and durability of CAR T responses while potentially improving the therapeutic window. The ongoing registrational studies, including the phase 2 iMMagine-1 trial, will determine whether this promising phase 1 signal translates into a clinically meaningful advantage for patients with multiple myeloma.

Natalie Rafaeli, MD is a specialist in malignant hematology, specifically with expertise in treating blood cancer. Dr. Rafaeli serves as an Assistant Professor in the McGovern Medical School Department of Internal Medicine. Her research focuses on developing novel treatment strategies. Dr. Rafaeli is board certified in Internal Medicine, Hematology, and Medical Oncology.

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