A new analysis suggests the combination of anti-B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies may achieve durable responses in patients with relapsed/refractory multiple myeloma (R/R MM). Results of the analysis were presented in a report in the Journal of Clinical Oncology.
The report was based on a long-term follow-up analysis of a single-arm phase 2 trial conducted in China that evaluated anti-BCMA and anti-CD19 CAR-T therapies in patients with R/R MM (Chinese Clinical Trial Registration Center Identifier: ChiCTR-OIC-17011272). Patients had been given conditioning chemotherapy that included cyclophosphamide and fludarabine before receiving anti-BCMA and anti-CD19 CAR T-cell therapies, which were each administered in a single dose of 1×106 cells/kg.
Overall response rate (ORR) was the primary endpoint of the study. The primary analysis was based on results obtained as of January 20, 2019, for 21 patients. The long-term analysis described further outcomes for these and additional patients, with results reported for a total of 62 patients who received both CAR-T therapies.
With a median follow-up of 21.3 months after CAR-T infusion, the ORR in this long-term analysis was 92%. A complete response (CR) or better was seen in 60% of patients. Very good partial response was reported in 19% of patients, and partial response was seen in 13%. Among 56 evaluable patients, 77% had confirmation of minimal residual disease (MRD) negativity.
Median duration of response for patients with partial response or better was estimated to be 20.3 months (95% CI, 9.1-31.5). Following CAR-T infusion, 0.9 months (range, 0.5 to 3.2) was the median time to MRD negativity. Time to MRD negativity did not appear associated with depth of response.
Median overall survival was not reached, and the median progression-free survival (PFS) time was 18.3 months (95% CI, 9.9-26.7). In patients with CR or better, the median PFS was not reached. Subgroup analyses revealed extramedullary disease to be associated with poorer survival outcomes.
Cytokine release syndrome (CRS) was reported in 95% of patients, with 10% experiencing CRS of grade 3 or higher. Neurotoxicity was reported in 11% of patients, with 3% experiencing neurotoxic events of grade 3 or higher. Adverse events occurring more than 3 months after CAR-T infusion were reported to be rare, with the exception of B-cell aplasia, hypogammaglobulinemia, and infections.
“In summary, long-term follow-up data showed that the combination of anti-BCMA and anti-CD19 CAR T-cells induced durable response in patients with R/R MM with a manageable long-term safety profile,” the study investigators concluded.
Wang Y, Cao J, Gu W, et al. Long-term follow-up of combination of B-cell maturation antigen and CD19 chimeric antigen receptor T cells in multiple myeloma. J Clin Oncol. Published online March 25, 2022. doi:10.1200/JCO.21.01676