Idecabtagene Vicleucel (ide-cel) Shows Similar Efficacy and Toxicity in Patients with Multiple Myeloma Aged 70 and Older Compared to Younger Patients: A Multicenter Cohort Study

Introduction

The introduction of B-cell maturation antigen (BCMA) directed chimeric antigen receptor-T (CAR-T) cell therapies have revolutionized the treatment landscape of relapsed/refractory (r/r) multiple myeloma (MM). Currently, two CAR-T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are approved for r/r MM and demonstrated remarkable efficacy in the pivotal trials. However, data on the efficacy and safety of these therapies in older patients - who often have more comorbidities and are frequently underrepresented in approval studies - remain limited. Real-world evidence is needed to complement clinical trial findings and report clinical practice and outcomes. We sought to fill this gap by evaluating the efficacy and toxicity profiles of patients aged 70 and older compared to their younger counterparts in a real-world setting.

Methods

We conducted a multicenter retrospective analysis including 136 relapsed/refractory MM pts without CNS manifestation undergoing CAR-T cell treatment with ide-cel between March 2022 and May 2024 at seven tertiary german centers. Patients were grouped by age at CAR-T infusion ((<70 vs. ≥70 years (yrs)). Subsequently, descriptive and survival analyses, including propensity score matching (nearest neighbor 1:1 matching with R-ISS stage, number of therapy lines, triple- and penta-class refractoriness, and remission status as co-variates), were performed to compare outcomes between both age groups.

Results

We identified 91 patients aged <70 and 45 patients aged ≥70 yrs. The median age was 61 yrs (range: 36-69 yrs) and 72 yrs (range: 70-82 yrs) at CAR-T infusion, respectively. Thirteen (9.6%) patients were aged ≥75 yrs. Both groups had similar proportions for ECOG score 0-2 (74.4% vs. 84.4%, p=0.27), R-ISS stage III at diagnosis (28.6% vs. 42.2%, p=0.38), high-risk cytogenetics (51.8% vs. 35.9%, p=0.12), median time from first diagnosis to CAR-T (6.9 vs. 8.0 years, p=0.26), penta-refractory status (51.6% vs. 62.2%, p=0.36), prior BCMA-directed therapy (14.4% vs. 15.6%, p=1.0), and prior autologous stem cell transplantation (93.4% vs. 86.7%, p=0.21). Both groups had a median of five prior treatment lines (p=0.49). There were no significant differences in disease status at CAR-T infusion regarding serologic CR and VGPR/PR (7.7% vs. 11.1% and 25.3% vs. 31.1%, both p=0.31). Both groups had a median of one bridging therapy line (p=0.65). Notably, extramedullary disease at CAR-T was more frequent in patients <70 yrs compared to those ≥70 yrs (37.6% vs. 14.0%, p=0.007).

Cytokine-release syndrome (CRS) grade 3-4 occurred in 7.7% of the younger group and 4.4% of the older group (p=0.71). For all grades of ICANS, there was a higher proportion in patients ≥70 yrs (24.4% vs. 6.6%, p=0.005), but no difference for ICANS grade 3-4 (0% vs. 2.2%, p=1.0). Tocilizumab usage was similar across both groups (p=0.16), as were infections within 30 days post-CAR-T (p=0.19), and lowest values of neutrophils (p=0.12), platelets (p=0.72), hemoglobin (p=0.95), and IgG (p=0.88).

Overall response rates considering CR/VGPR/PR were comparable for both age groups (87.8% vs. 92.7%; p=0.274). With a median follow-up of 8.1 months, median progression-free survival (PFS) was 9.2 months (95%-CI: 6.7-14.1) for the younger group and 9.6 months (95%-CI: 6.9-NR) for the older group (p=0.39), with 1-year PFS rates of 42.9% and 48.7%, respectively. Median overall survival (OS) was not reached; 1-year OS was 67.1% and 66.8% (p=0.95). Additionally, no significant differences were noted in the cumulative incidence of 1-year non-relapse mortality (p=0.17) and cumulative relapse incidence (p=0.08) between the age groups. These results were consistent in the propensity score-matched cohort of 80 patients. In a multivariate regression analysis considering age groups, number of treatment lines, and disease status prior to CAR-Ts as covariates, only extramedullary disease at CAR-T was associated with decreased PFS (HR=1.96, 95%CI: 1.11-3.48, p=0.021).

Conclusions

With the paucity of long-term data, our real-world analysis provides additional support that CAR-T cell therapy is feasible and effective in patients with r/r MM aged 70 yrs or older, demonstrating outcomes and toxicities comparable to those observed in younger patients. Therefore, CAR-T cell therapy should not be withheld for eligible patients above 70 yrs with r/r MM.

Schultze-Florey:Janssen: Consultancy, Honoraria, Other: Travel support, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Other: Travel support; Pierre Fabre: Consultancy, Honoraria, Other: Travel support; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Abbvie: Other: Travel support. Schub:BMS, Janssen: Honoraria. Daskalakis:Kite Gilead, Novartis: Other: Travel and congress support ; Novartis: Consultancy, Honoraria. Knust:Sanofi, Janssen, GSK: Consultancy; GSK, Sanofi, Janssen: Honoraria; Janssen, Amgen, Abbvie: Research Funding. Stelljes:Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria; Medac: Honoraria, Other: Travel- & congress-support; Amgen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Takeda: Consultancy; Incyte: Consultancy, Honoraria; BMS: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Travel- & congress-support, Research Funding; Gilead: Honoraria; Celgene: Honoraria; Abbvie: Honoraria. Heidel:Novartis, Celgene/BMS, CTI: Research Funding; BMS/Celgene, AOP, Novartis, CTI, Janssen, Abbvie, GSK, Merck, CTI, Kartos, Telios: Consultancy. Reinhardt:Abbvie, AstraZeneca, Vertex and Merck: Consultancy, Other: lecture fees ; AstraZeneca, Gilead Pharmaceuticals: Research Funding; CDL Therapeutics GmbH: Other: Co-founder. Lenz:Gilead: Honoraria, Research Funding; AQUINOX: Research Funding; Immagene: Honoraria; Incyte: Honoraria; Karyopharm: Honoraria; Lilly: Honoraria; Miltenyi Biotech: Honoraria; MSD: Honoraria; NanoString: Honoraria; PentixaPharm: Honoraria; Pierre Fabre: Honoraria; Sobi: Honoraria, Speakers Bureau; Acerta: Research Funding; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Consultancy; ELVESCA: Current equity holder in private company; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Membership on an entity's Board of Directors or advisory committees; AbbVie, BeiGene, Sobi, Roche, Gilead, BMS: Other: Travel; Constellation: Honoraria; Genase: Honoraria; Genmab: Honoraria; Hexal/Sandoz: Honoraria; Roche: Honoraria, Research Funding; Verastem: Research Funding; ADC Therapeutics: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; BeiGene: Honoraria; BMS: Honoraria; AstraZeneca: Honoraria, Research Funding; MorphoSys: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; AGIOS: Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. von Tresckow:AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis: Other: Travel and congress support ; Esteve (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), and Takeda (Inst): Research Funding; AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche and Takeda: Honoraria; Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Regeneron, Roche, Sobi and Takeda: Consultancy. Shumilov:Oncopeptides: Consultancy, Honoraria, Other: Travel and congress support; Stemline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and congress support; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and congress support; BMS: Consultancy, Honoraria; Incyte: Honoraria; Sanofi-Aventis: Consultancy, Honoraria, Other: Congress support.