KarMMa-3 trial of ide-cel vs SOC in RRMM meets its primary endpoint

On August 10, 2022, positive topline results were announced from the phase III KarMMa-3 trial (NCT03651128), which is comparing idecabtagene vicleucel (ide-cel) with standard combination regimens in patients with multiple myeloma that has been treated with two to four prior lines of therapy and is refractory to the last regimen.¹

Following the prespecified interim analysis, it’s been established that the trial has met its primary endpoint of a statistically significant improvement in progression-free survival with ide-cel. Of note, this is the first randomized trial of a chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma to communicate positive results. Further data from the KarMMa-3 trial will be released in a scientific conference soon.¹

Idecabtagene vicleucel¹

In March 2021, ide-cel became the first B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy approved by the U.S. Food and Drug Administration (FDA) following data from the KarMMA trial. Similarly, ide-cel was granted a conditional marketing license by the European Commission (EC) in August 2021. Ide-cel is licensed for use after ≥4 prior lines of therapy by the FDA and ≥3 prior lines of therapy by the EC.

KarMMa-3 trial

The design of the KarMMa-3 trial, including inclusion/exclusion criteria and efficacy measures, can be seen Figure 1.

Figure 1. Design of the KarMMa-3 trial* 

allo-SCT, allogeneic stem cell transplant; auto-SCT, autologous stem cell transplant; BCMA, B-cell maturation antigen; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CR, complete remission; DOR, duration of response; DPd, daratumumab, pomalidomide, dexamethasone; DVd, daratumumab, bortezomib, dexamethasone; EPd, elotuzumab, pomalidomide, dexamethasone; ide-cel, idecabtagene vicleucel; IRd, ixazomib, lenalidomide, dexamethasone; ECOG, Eastern Cooperative Oncology Group; EFS, event-free survival; IMiD, immunomodulatory imide drug; Kd, carfilmozib, dexamethasone; MM, multiple myeloma; MRD, minimal residual disease; NGS, next-generation sequencing; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; POEMS,  polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes; PS, performance status; RRMM, relapsed/refractory multiple myeloma.
*Data from ClinicalTrials.gov.²

 Results¹

This trial plans to recruit a total of 381 patients aged ≥18 years. The prespecified interim analysis demonstrated a statistically significant improvement in progression-free survival with ide-cel compared with traditional regimens, as well as improved overall response rates and overall survival rates. In addition, the safety and tolerability of ide-cel was reported to be consistent with prior clinical trial data. Further endpoint data are anticipated.

Of note, initial data from a multicenter study of ide-cel in a real-world setting were recently reported by Doris Hansen at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. In the video below, Hansen discusses these initial data from a total of 159 patients.