Anitocabtagene Autoleucel iMMagine-1 Trial: Exceptional Safety and Durability in Relapsed Myeloma

Описание: The Phase 2 iMMagine-1 registrational trial evaluated anitocabtagene autoleucel (anito-cel), an anti-BCMA CAR-T therapy featuring a novel D-domain binder with unique attributes including small size, simple structure, and fast off-rate designed to enhance transduction efficiency and reduce tonic signaling risks. Among 117 heavily pretreated patients with relapsed/refractory multiple myeloma (median 5 prior lines, 86% triple-class refractory, 40% penta-drug refractory) followed for a median 12.6 months, the investigator-assessed overall response rate reached 97% with 68% complete response/stringent complete response rate and median time to first response of only 1 month. Remarkably, 93% of evaluable patients (70/75) achieved MRD negativity at sensitivity of 1 in 100,000, with 78% achieving ultra-sensitive MRD negativity at 1 in 1,000,000, both occurring at median 1 month post-infusion. The progression-free survival rates at 12 and 18 months were 79% and 66% respectively, with overall survival rates of 95% and 90%, while median PFS and OS have not been reached. Most notably, the safety profile showed no delayed neurotoxicity including zero cases of Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome across both Phase 1 and Phase 2 studies, no immune effector cell-associated enterocolitis, mild cytokine release syndrome (85% Grade 1 or less, 97% resolved within 10 days), minimal ICANS (8% any grade, only 1% Grade 3), and manageable cytopenias, establishing anito-cel as potentially best-in-class for safety among BCMA-targeted CAR-T therapies.

Key Points:

Exceptional Response Rates: 97% overall response rate (114/117) with 68% complete response/stringent complete response (79/117), achieved rapidly at median 1 month from infusion (range 0.9-13.4 months)
Universal Deep MRD Negativity: Among 75 evaluable patients, 93% achieved MRD negativity at 1 in 100,000 sensitivity and 78% at ultra-sensitive 1 in 1,000,000 sensitivity, both at median 1 month, representing among the highest and fastest MRD negativity rates reported for CAR-T therapy
Durable Disease Control: 12-month and 18-month PFS rates of 79% and 66% with median PFS not reached; 12-month and 18-month OS rates of 95% and 90% with median OS not reached after 12.6 months median follow-up
Zero Delayed Neurotoxicity: Across both Phase 1 (38.1 months median follow-up) and Phase 2 studies, no cases of Parkinsonism, cranial nerve palsies, Guillain-Barré syndrome, or any non-ICANS neurotoxicity observed, distinguishing anito-cel from other BCMA CAR-T products
Minimal ICANS: Only 8% experienced any grade ICANS (4 Grade 1, 4 Grade 2, 1 Grade 3), dramatically lower than typical 10-20% rates seen with other BCMA CAR-T therapies
Mild, Transient CRS: 85% experienced Grade 1 or less CRS (including 15% with no CRS), 97% had CRS resolution within 10 days of infusion, median onset day 4 with median duration 2 days; only one Grade 5 CRS event
Manageable Blood Counts and Infections: Grade 3/4 cytopenias included neutropenia (66%), anemia (24%), and thrombocytopenia (24%); Grade 3/4 infections occurred in only 9% of patients
No IEC-Associated Complications: Zero cases of immune effector cell-associated enterocolitis or secondary T-cell origin malignancies reported across both trials
Heavily Pretreated Population: Median 5 prior lines (range 3-8) with 51% receiving only 3 prior lines, 100% refractory to last line, 86% triple-class refractory, 40% penta-drug refractory, 38% high-risk cytogenetics, 15% extramedullary disease
Outpatient Feasibility: 9% of patients (10/117) received outpatient infusion, demonstrating favorable safety profile allows for non-hospital-based administration

Conclusion:
The Phase 2 iMMagine-1 trial positions anitocabtagene autoleucel (anito-cel) as potentially the safest and most effective BCMA-targeted CAR-T therapy for relapsed/refractory multiple myeloma. The novel D-domain binder technology delivers exceptional efficacy with a 97% response rate, 68% complete response, and 93% MRD negativity at ultra-sensitive levels within one month. Critically, anito-cel demonstrates complete absence of delayed neurotoxicity including zero Parkinsonism cases across both Phase 1 and Phase 2 studies, a meaningful advance over existing CAR-T products where delayed neurotoxicity affects 10-12% of patients. The remarkably low 8% ICANS rate, predominantly mild CRS resolving within days, and feasibility of outpatient administration suggest the unique molecular design—featuring fast off-rate kinetics—reduces on-target/off-tumor toxicity while maintaining superior anti-myeloma activity. Durable control is evident with 79% progression-free survival at 12 months in heavily pretreated patients.