KarMMa-3 subgroup analysis in older patients with relapsed/refractory multiple myeloma treated with idecabtagene vicleucel

Abstract Introduction: Chimeric antigen receptor (CAR) T-cell therapies are an effective treatment option for patients with relapsed/refractory multiple myeloma (RRMM). Idecabtagene vicleucel (ide-cel) is a B-cell maturation antigen-targeted CAR T-cell therapy approved for patients with RRMM with ≥2 prior lines of therapy. Developing a better understanding of the relationship between patient age and CAR T-cell therapy outcomes may help guide treatment and clinical practice. This analysis of data from the KarMMa-3 trial (NCT03651128) describes efficacy and safety outcomes in older and younger patients who received either ide-cel or standard therapy regimens. Methods: KarMMa-3 is an open-label, phase 3 trial that includes adults with RRMM who have received 2-4 prior treatment regimens with disease refractory to the last therapy. Enrolled patients were randomized (2:1) to receive either a one-time infusion of ide-cel or 1 of 5 standard regimens. This subgroup analysis evaluated the efficacy and safety of ide-cel compared with standard regimens in KarMMa-3 patients by age group (≥70 vs <70 yrs). Outcome measures assessed include overall response rate (ORR), progression-free survival (PFS), overall survival (OS), patient-reported quality of life (QoL), and incidence of selected adverse events. Results: A total of 386 patients were evaluated; 19.3% (49/254) of those receiving ide-cel and 20.5% (27/132) of those receiving standard regimens were aged ≥70 yrs. Compared with older patients, younger patients receiving ide-cel exhibited more high-risk baseline characteristics, including high-risk cytogenic abnormalities (44.4% vs 32.7%) and triple-class refractory disease (66.8% vs 55.1%). The median time to progression during the most recent prior anti-myeloma treatment was longer for patients aged ≥70 yrs who received ide-cel vs standard regimens (8.6 mo vs 6.7 mo) but was similar for patients aged <70 yrs (6.5 mo vs 6.9 mo). ORR for patients aged <70 yrs was 68.8% (95% CI: 62.4, 75.1) with ide-cel and 41.0% (95% CI: 31.5, 50.4) with standard regimens (P<0.0001). Patients aged ≥70 yrs treated with ide-cel achieved an ORR of 81.6% (95% CI: 70.8, 92.5) vs 48.1% (95% CI: 29.3, 67.0) with standard regimens (P<0.01). Median PFS for patients aged <70 yrs was longer with ide-cel treatment vs standard regimens (12.5 mo [95% CI: 11.2, 15.4] vs 4.2 mo [95% CI: 3.5, 5.7]; P<0.0001). Similar trends were seen in patients aged ≥70 yrs, where median PFS was 18.9 mo (95% CI: 12.1, 24.5) with ide-cel treatment and 5.7 mo (95% CI: 2.2, 12.2) with standard regimens (P<0.01). Median OS was not reached in older patients in either treatment arm; in younger patients, median OS was 39.5 mo (95% CI: 27.8, NR) with ide-cel and 27.9 mo (95% CI: 20.6, NR) with standard regimens. Incidence of adverse events reported with ide-cel treatment was generally similar between age groups for cytokine release syndrome, neurotoxicity, and infections. Analyses of patient-reported QoL data and other relevant safety endpointsare ongoing and will be included in the presentation. Conclusions: In the KarMMa-3 trial, patients aged ≥70 years derived substantial benefit from ide-cel treatment, demonstrated by longer PFS and a notable ORR compared with standard regimens. While efficacy and safety outcomes of ide-cel treatment in older patients were consistent with younger patients, it is important to note that patients in the trial aged ≥70 yrs were more likely to have favorable baseline characteristics and less aggressive and heavily pretreated disease. This may reflect a selection bias towards enrolling older patients considered to be easier to treat. In contrast, real-world data from late-line settings suggest that older patients are undergoing treatment based on less restrictive selection criteria—eg, including those with higher-risk baseline features—reflecting a more representative and broader population. These observations reinforce the potential for durable benefit with a single ide-cel infusion in a real-world context without additional adverse safety signals, supporting its use across age groups.