Anitocabtagene Autoleucel Demonstrates Deep, Durable Responses and Improved MRD-Negativity in RRMM

Anitocabtagene autoleucel (anito-cel; Arcellx, Inc) demonstrated durable efficacy and manageable safety in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM), according to data from the iMMagine-1 (NCT05396885) presented at the 2025 International Myeloma Society Annual Meeting in Toronto, Canada.¹

Treatment for patients with RRMM has greatly improved over the past decade with the emergence of novel immunotherapies, not limited to bispecifics and chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is an immunotherapy that uses the body’s own immune system to fight cancer. The process involves collecting T-cells from patients and manufacturing them to target specific antigens, such as BCMA or GPRC5D, before reintroducing them to the body. This helps the body’s immune cells to better recognize cancer cells from normal, healthy cells.²

Anito-cel is an autologous CAR T-cell therapy that targets BCMA, the most commonly overexpressed protein on the surface of myeloma cells. The agent is unique compared with other CAR T options due to its novel D-domain binder. Although under continued development, the agent demonstrates clinically meaningful outcomes in the phase 2, open-label iMMagine-1 trial.³

The trial involved patients with RRMM who were triple class exposed and had progressed following 3 or more lines of therapy (LOT). Patients received lymphodepletion chemotherapy and a single infusion of anito-cel following leukapheresis, optional bridging, and anito-cel manufacturing.

The primary end point is overall response rate (ORR) by Independent Review Committee and assessed using 2016 IMWG. MRD was measured using next-generation sequencing. Toxicity was graded based on CTCAE version 5.0, and cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded by the American Society for Transplantation and Cellular Therapy consensus criteria.⁴

A total of 86 patients received anito-cel, each with at least 2 months of follow-up. Median follow-up was 9.5 months (range, 2–23). Patients had received a median of 4 LoT (range, 3–8), with 43% (n = 37) having received only 3 prior LoT. The majority of patients were heavily pretreated, with 86% (n = 74) classified as triple-class refractory and 43% (n = 37) as penta-drug refractory.⁴

The ORR was 97% (83/86), with a complete response or stringent complete response achieved in 62% (53/86). Among patients evaluable for MRD, (n = 58), 93.1% (54/58) reached MRD negativity at a sensitivity of at least 10⁻⁵, with a median time to MRD negativity of one month (range, 1–6). By Kaplan-Meier estimates, 12-month duration of response (DoR), progression-free survival (PFS), and overall survival (OS) rates were 75.6%, 78.5%, and 96.5%, respectively. Median DoR, PFS, and OS were not reached at the time of analysis.⁴

The most common grade 3 or higher treatment-emergent adverse events were cytopenias. CRS occurred in 83% (n = 81), most of which were low grade: 68% grade 1, 13% grade 2, and 1% grade 5. Seventeen patients (17%) experienced no CRS, and overall, 98% (96/98) had either no CRS or resolution within 14 days of infusion. Median CRS onset was 4 days (range, 1–17), with a median duration of 3 days (range, 1–9).⁴

Rates of ICANS were much lower at 9% (n = 9), including 4 grade 1, 4 grade 2, and 1 grade 3 events. No delayed or atypical neurotoxicities were observed, including no Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome.⁴

REFERENCES

1. Study of anitocabtagene-autoleucel in relapsed or refractory multiple myeloma (iMMagine-1) (iMMagine-1). Clinicaltrials.gov. Updated July 16, 2025. Accessed September 23, 2025. https://clinicaltrials.gov/study/NCT05396885

2. CAR T-cell therapy and its side effects. American Cancer Society. July 7, 2025. Accessed September 23, 2025. https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell.html

3. Gerlach A. Anitocabtagene autoleucel yields overall response rate of 97% in patients with multiple myeloma. Pharmacy Times. May 14, 2025. Accessed September 23, 2025. https://www.pharmacytimes.com/view/anitocabtagene-autoleucel-yields-overall-response-rate-of-97-in-patients-with-multiple-myeloma

4. Kaur G, Freeman C, Dhakal B, et al. Phase 2 registrational study of anitocabtagene autoleucel for relapsed and/or refractory multiple myeloma (RRMM): Updated results from iMMagine-1. 2025 International Myeloma Society Annual Meeting. Toronto, Canada. Abstract PA-288