In a retrospective study of the real-world use of idecabtagene vicleucel reported in the Journal of Clinical Oncology, Hansen et al found that response rates and toxicity in patients with relapsed or refractory multiple myeloma were comparable to those in the pivotal phase II KarMMa trial; the majority of patients treated in the real-world setting would have been ineligible for KarMMa on the basis of comorbidities at the time of leukapheresis.
KarMMa supported the March 2021 approval of idecabtagene vicleucel for heavily pretreated relapsed or refractory multiple myeloma; idecabtagene vicleucel was the first autologous B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy approved in this setting.
Study Details
The current study involved data on 196 patients who underwent leukapheresis as of the end February 2022 at 11 U.S. institutions in the Myeloma CAR T Consortium with the intent of receiving standard-of-care idecabtagene vicleucel under the commercial U.S. Food and Drug Administration label.
In KarMMa, the overall response rate was 73%, with complete response or better seen in 33% of patients. Cytokine-release syndrome was observed in 84% of patients and was grade ≥ 3 in 5%; neurotoxicity was observed in 18% of patients and was grade ≥ 3 in 3%. Median progression-free survival was 8.8 months, and estimated median overall survival was 19.4 months.
Real-World Findings
In the current study, a total of 159 of the 196 patients undergoing leukapheresis received idecabtagene vicleucel by data cutoff. Of the 159, 120 (75%) would have been ineligible for participation in KarMMa on the basis of comorbidities at time of leukapheresis. The most common reasons for ineligibility were inadequate organ function (28%), prior use of BCMA-targeted therapy (21%), cytopenias (neutropenia in 14%, anemia in 16%, thrombocytopenia in 21%), and an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 (18%).
The overall response rate was 84%, with complete response or better seen in 42% of patients.
Cytokine-release syndrome was observed in 82% of patients and was grade ≥ 3 in 3%. Neurotoxicity was observed in 18% of patients and was grade ≥ 3 in 6%.
At a median follow-up of 6.1 months from CAR T-cell infusion, median progression-free survival was 8.5 months (95% confidence interval [CI] = 6.5 months to not reached) and median overall survival was 12.5 months (95% CI = 11.3 months to not reached).
On multivariate analysis, factors associated with poorer progression-free survival included previous vs no previous exposure to BCMA-targeted therapy (hazard ratio [HR] = 2.81, P = .003); high-risk vs no high-risk cytogenetics (HR = 2.31, P = .003); and ECOG performance status of 2 to 4 vs 0 or 1 at lymphodepletion (HR = 2.19, P = .016).
The investigators concluded, “The safety and efficacy of idecabtagene vicleucel in patients with relapsed or refractory multiple myeloma in the standard-of-care setting were comparable with those in the phase II pivotal KarMMa trial, despite most patients not meeting trial eligibility criteria.”
Doris K. Hansen, MD, of the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
