Ide-cel Significantly Prolongs PFS in KarMMa-3 Trial for Multiple Myeloma
Paula Rodriguez-Otero, MD, PhD, provides an overview of the phase 3 KarMMa-3 trial of idecabtagene vicleucel for the treatment of adult patients with relapsed and refractory multiple myeloma.
Paula Rodriguez-Otero, MD, PhD, University Clinic of Navarra, Pamplona, Spain, provides an overview of the methods, design, and findings from the phase 3 KarMMa-3 trial (NCT03651128) of idecabtagene vicleucel (ide-cel; Abecma) for the treatment of adult patients with relapsed and refractory multiple myeloma who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Transcription:
0:09 | In this presentation we presented the planned final progression-free survival [PFS] analysis and also the first disclosure of the interim overall survival with a median follow-up of 30.9 months. Regarding the primary end point of the study which was progression-free survival, with the extended follow-up, ide-cel continued to show a significant improvement in the progression-free survival with a median PFS of 13.8 months vs 4.4 months in the standard regimen arm with a hazard ratio of 0.49. That means a 51% reduction in the risk of progression and death.
0:52 | Also with the extended follow-up, the overall response rate continued to be superior with ide-cel as compared with a standard regimen, so 71% vs 42%, and so are the complete response and the [minimal residual disease (MRD)]-negative rate. They were also higher in the patients assigned to the ide-cel arm. Regarding the first disclosure of the overall survival data, with a median follow-up close to 31 months, the median overall survival in the ide-cel arm was 41.4 months and the median overall survival in the standard regimen arm was 37.9 months with a hazard ratio of 1.01.
1:38 | It is important to understand that when we evaluate this overall survival data that there are several factors. First, the study design was not planned to give a definitive conclusion regarding overall survival. Overall survival was a secondary end point and this study did not have the statistical power to show that difference in overall survival. More importantly, the study design, which allowed for crossover for patients assigned to the standard regimen arm, clearly confounds the survival interpretation. It is important to know that 56% of the patients that were initially assigned to the standard regimen arm had or already received ide-cel infusion after crossover, and this could happen as early as by month 3, with a median time from randomization to ide-cel infusion in patients in the standard arm of 8.1 months. When we evaluate the preplanned sensitivity analysis, adjusting for crossover in this study, the hazard ratio is 0.72 in favor of ide-cel. These are important key takeaways of this study.
