Dr Bal on Ide-cel in R/R Multiple Myeloma

Susan Bal, MD, assistant professor, University of Alabama at Birmingham, discusses key efficacy and safety data from the phase 2 KarMMa trial (NCT03361748) in patients with relapsed/refractory multiple myeloma.

The second-generation CAR T-cell product idecabtagene vicleucel (ide-cel; Abecma) was the first anti-BCMA CAR T-cell therapy to be FDA approved for patients with relapsed/refractory multiple myeloma. This product, which was granted FDA approval on March 26, 2021, has a CD3 zeta cell activation domain and has a costimulatory domain from 4-1BB. The FDA approval of ide-cel was based on findings from the KarMMa trial, which evaluated the efficacy and safety of this agent at doses ranging from 150 x 10⁶ to 450 x 10⁶ CAR-positive T cells.

KarMMa enrolled 140 patients, 128 of whom received ide-cel. In total, 84% of the treated patients were triple-class refractory, and the median age was 61 years, which is younger than the typical median age of patients with multiple myeloma, Bal says. The treated population had received a median of 6 prior lines of therapy.

CAR T-cell therapy has unique adverse effects, including cytokine release syndrome (CRS), which 84% of patients experienced in the trial, Bal notes. However, the CRS events observed in this trial were mostly grade 1 or 2, with 5 patients experiencing grade 3 CRS and 1 patient each experiencing grades 4 and 5 CRS.

Neurotoxicities were also observed in this study, but at a lower frequency than is often seen in patients with lymphoma, Bal explains. Overall, 18% of patients experienced any-grade neurotoxicity, and 3% of patients experienced grade 3 neurotoxicity.

In total, ide-cel generated an overall response rate (ORR) of 73% in the overall study population and an ORR of 81% in patients who had received the highest dose level. Additionally, 33% of patients in the overall population achieved a complete response.

The median progression-free survival was 8.8 months in the entire study population and 12.1 months in the patients who received the highest dose level. Furthermore, the median overall survival was 19.4 months in the entire study population, Bal concludes.