Patients had an ORR of 83.8% with a median DOR of 15.7 months in data presented at the ASH 2022 meeting.
Idecabtagene vicleucel (ide-cel; Abecma; Bristol Myers Squibb; bluebird bio) induced deep responses in patients with clinically high-risk, early relapsed multiple myeloma after frontline autologous stem cell therapy enrolled in cohort 2a of the phase 2 KarMMa-2 study (NCT03361748).
These new data from KarMMa-2 were presented at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, 2022, in New Orleans, Louisiana, by Krina Patel, MD, MSc, Associate Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
“Patients who have high-risk disease have certain characteristics like high-risk cytogenetics and extramedullary disease, but those who relapse really early after frontline therapy, after stem cell transplant especially, have high risk features and have markedly inferiorsurvivalversus those who relapse later...Therapies with novel mechanisms of action are really needed to improve outcomes for these vulnerable patients with unmet needs,” Patel said during her presentation. “Most of my high-risk patients can’t get to that fifth line [that ide-cel is approved for in the US].”
Data from 37 patients in cohort 2a of the KarMMA-2 study were presented who received a median dose of 425x106 chimeric antigen receptor (CAR) T-cells (range, 300.2-525.6x106). Two additional patients were enrolled in the cohort and underwent leukapheresis, with 1 discontinuing due to physician decision and the other withdrawing consent. Out of the 37 patients infused, 15 more discontinued due to death (n = 4; 10.8%), patient withdrawal (n = 9; 24.3%), or physician decision (n = 2; 5.4%).These patients had a median age of 57.0 years (range, 36.0-77.0).
As of the data cutoff date of March 14, 2022, median follow-up was 21.5 months (range, 2-31), with 73% of patients having at least 1 year of follow-up, and 22 patients (59.5%) are ongoing in the study. Out of these 22 evaluable patients, 12 had high-risk cytogenetics at baseline and 4 had ultra-high-risk cytogenetics. Only 24.3% had had a complete response (CR) to frontline therapy.
KarMMA-2 continued to meet its primary endpoint in this cohort, with 45.9% of patients achieving at least a CR (P <.0001). The overall response rate (ORR) was 83.8% (95% CI, 68.0-93.8) and median time-to-response was 1.0 month (range, 0.9-2.9). The median duration of response (DOR) in all responders was 15.7 months (95% CI, 7.6-19.8) while the median DOR in patients with at least a CR was 23.5 months (95% CI, 10.2-not estimable [NE]). Patients with a very good partial response had a median DOR of 7.5 months (95% CI, 0.6-14.4) and those with a partial response had a median DOR of 3.0 months (95% CI, 1.0-NE).
Median progression-free survival was 11.4 months (95% CI, 5.6-19.6) and median overall survival (OS) was not reached. At 24 months, the OS event-free rate was 84.7% (standard error, 6.31). Minimal residual disease (MRD) negativity was observed in 85% of evaluable patients with at least a CR at 6 months post-infusion and 70% of these patients at 12 months. Cell expansion was greater in patients with at least a CR than those without. Soluble BCMA was cleared within 2 months in 67.6% of patients (n = 25) and in all patients that had a CR.
Most patients had grade 3/4 neutropenia with a median recovery time of 1.45 months (95% CI, 1.45-1.87). Two patients died due to adverse events (AEs) of pneumonia and pseudomonal sepsis. Most patients (81.8%) had cytokine release syndrome (CRS) managed with tocilizumab and corticosteroids but only 1 patient had grade 3 CRS. Investigator-identified neurotoxicity occurred in 21.8% of patients (n = 8) and all cases were grades 1/2.
“In this analysis of our cohort 2a KarMMa-2 trial, ide-cel demonstrated a frequent deep response in patients with clinical high-risk myeloma who experienced early relapse within 18 months of frontline therapy which included stem cell transplant...In these difficult to treat patients, these high response rates are encouraging. This supports a favorable clinical benefit-risk profile for ide-cel in a clinically high-risk patient population and its potential use in earlier lines of treatment for this population with this unmet need,” Patel concluded.