The phase II registrational IMMagine-1 trial has revealed promising results for anitocabtagene autoleucel, a novel anti-BCMA CAR T-cell therapy, in treating heavily pretreated patients with relapsed or refractory multiple myeloma. With a median follow-up of 9.5 months, the therapy demonstrated an exceptional investigator-assessed overall response rate of 97%, with 62% of patients achieving a complete response or better.
Unprecedented Response Rates and Early Survival Data
The single-arm study, which enrolled 117 patients who had received at least three prior lines of therapy, showed remarkable efficacy. A striking 93% of evaluable patients achieved measurable residual disease (MRD) negativity at a sensitivity of 10-5, with a median time to MRD negativity of just one month.
Preliminary survival data appears promising, with an estimated 6-month progression-free survival of 93.3% and 12-month progression-free survival of 78.5%. The estimated overall survival rate at both 6 and 12 months stood at 96.5%, though median overall survival has not yet been reached.
"Anitocabtagene autoleucel, with its novel D-domain binder and enhanced CAR T-cell transduction efficiency, shows remarkable efficacy in this challenging population and is a promising, novel therapeutic option," said lead study author Dr. Ciara Freeman of the Moffitt Cancer Center.
Safety Profile and Adverse Events
The therapy demonstrated a manageable safety profile, with most patients experiencing only grade 1 or 2 cytokine-release syndrome (CRS). While CRS occurred in 83% of patients, severe cases (grade ≥ 3) were reported in just 2%. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 9% of patients, with all cases resolving without long-term effects.
The most common severe adverse events included cytopenias, such as low white blood cell counts and anemia. Three deaths occurred during the trial, including one from an inflammatory storm related to rapidly progressing disease and another from an invasive fungal infection.
Future Directions
Building on these promising results, enrollment is currently underway for the phase III IMMagine-3 trial, which will compare anitocabtagene autoleucel with standard-of-care therapies in patients with one to three prior lines of treatment.
"These early results are very encouraging for patients and continue to build on what we know about how effective these personalized therapies can be for patients with multiple myeloma, even in those where multiple prior treatments have failed," Dr. Freeman concluded.
The innovative approach of anitocabtagene autoleucel, particularly its novel D-domain binder and enhanced CAR T-cell transduction efficiency, represents a significant advancement in the treatment landscape for multiple myeloma, potentially offering new hope for patients who have exhausted other treatment options.
