Equecabtagene autoleucel (eque-cel), an investigational fully human-derived BCMA-targeting CAR-T cell therapy, has demonstrated significant efficacy in treating relapsed or refractory multiple myeloma, according to results from the FUMANBA-1 trial. The study, conducted across 14 centers in China, included both CAR-T naive and CAR-T experienced patients, highlighting the therapy's potential in a broad patient population.
The phase 1b/2 nonrandomized trial (ChiCTR2000033946) involved 103 patients who received a single infusion of eque-cel at 1.0 x 106 CAR-positive T cells/kg following lymphodepletion. All patients had received at least three prior lines of therapy. The primary outcome was the overall response rate (ORR), with secondary outcomes including safety, pharmacokinetics, and pharmacodynamics. Minimal residual disease (MRD) status was assessed to evaluate the depth of response. Patients will be followed for 15 years for long-term monitoring.
Efficacy Outcomes
The median follow-up was 13.8 months (range, 0.4-27.2 months). The ORR was 96% in the overall cohort and 99% among CAR-T naive patients. The median time to first response was 16 days (range, 11-179 days), and the median time to best response was 92 days (range, 14-557 days). At 3 months post-infusion, the ORR was 94.1%, with 42.6% achieving a complete response (CR) or stringent complete response (sCR). By 12 months, the CR/sCR rate increased to 73.3%, and was 79% in CAR-T naive patients.
The MRD negativity rate was notably high at 95%, with a median time to MRD negativity of 15 days (range, 14-186 days). Among patients achieving MRD negativity, the CR rate was 75%, and the sCR rate was 42%.
Median progression-free survival (PFS) and overall survival (OS) were not reached. However, the 12-month PFS rate was 78.8% (95% CI, 68.6%-86.0%), and the 12-month OS rate was 92.2% (95% CI, 84.3%-96.2%). CAR-T naive patients demonstrated superior ORR and PFS compared to CAR-T experienced patients.
Safety Profile
Adverse events (AEs) were common, with 102 patients experiencing AEs, 94.2% of which were grade 3 or higher. Common AEs included neutropenia (81.6%), leukopenia (74.8%), thrombocytopenia (59.2%), lymphopenia (59.2%), and anemia (51.5%). Cytokine release syndrome (CRS) was observed in most patients (grade 1/2, 92.2%; grade 4, 1%), with a median duration of 5 days (IQR, 4-7 days) and a median time to onset of 6 days (IQR, 4-7.5 days). Serious infection-related AEs occurred in 32 patients, and 14 patients died.
The study authors noted that impaired humoral immunity, characterized by prolonged B-cell depletion and hypogammaglobulinemia, contributed significantly to the infections. Strategies were implemented during the study to prevent infections.
Median recovery times for neutropenia and thrombocytopenia were 13 days (95% CI, 12-14 days) and 30 days (95% CI, 20-46 days), respectively.
Regulatory and Clinical Significance
Eque-cel has received five investigational new drug (IND) approvals from the FDA for use in systemic lupus erythematosus, lupus nephritis, multiple sclerosis, and myasthenia gravis. It has also received two IND approvals from China’s National Medical Products Administration for relapsed/refractory multiple myeloma and neuromyelitis optica spectrum disorder.
The authors highlighted the study's strengths, including the largest Asian population in a CAR-T trial and the notable response in patients with prior BCMA CAR-T exposure. Limitations included the absence of a comparator arm and a low number of patients with prior autologous stem cell transplants. Future studies with larger, more diverse populations and longer follow-up are warranted.
