Session: 655. Multiple Myeloma: Cellular Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, Real-world evidence, Lymphoid Malignancies
Methods This is the first international European study on the comparative efficacy and safety cilta-cel versus ide-cel in RRMM. We included only patients infused after 3 or more lines of therapy according to current approval. CAR-T expansion and persistence was measured at day 7, 14, 30, 90, and last follow-up by PCR or FACS, as per center’s practice. Co-primary endpoints were overall response rate (ORR) and progression-free survival (PFS). Secondary endpoints were complete response rate, overall survival (OS), incidence of cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS), and non-relapse mortality.
Results The total cohort included 162 with ide-cel and 42 with cilta-cel. Median age at time of CAR-T infusion was 61 years (range, 28 to 82 years) for ide-cel versus 61 years (range, 24 to 84 years) for cilta-cel (P=0.32). Median time between diagnosis and CAR-T infusion was 7.5 years for ide-cel versus 6.8 years for cilta-cel (P=0.53), and median turnaround time between apheresis and CAR-T infusion was 47 days for ide-cel versus 68 days for cilta-cel (P<0.001). Median number of prior lines of therapy was 6 for both groups and 15% in the ide-cel group versus 11% in the cilta-cel group had prior exposure to BCMA-directed therapy. Most patient characteristics were well balanced between both groups.
Cilta-cel showed deep and significantly higher ORR of 93% versus 79% for ide-cel (P<0.001). Early response appeared to be deeper for cilta-cel, showing complete response at day 30 after CAR-T infusion of 48% in the cilta-cel group versus 26% in the ide-cel group (P<0.001).
After a median follow-up of 9.5 months in the cilta-cel group versus 13.4 months in the ide-cel group (P<0.001), the 10-month PFS was 40% in the ide-cel group versus 75% in the cilta-cel group (P<0.001). The 10-month OS was 86% in the cilta-cel group versus 77% in the ide-cel group (P=0.11). Cilta-cel was independently associated with improved PFS and OS after multivariable adjustment.
The incidence of CRS was similar between both treatment groups (P=0.51), with 81% in the cilta-cel group versus 84% in the ide-cel group showing CRS of any grade after CAR-T infusion. Half of the patients in both groups had grade 1 CRS, while 9% in the cilta-cel groups versus 4% in the ide-cel group showed CRS grade 3-4. Onset of CRS appeared to be significantly earlier in the ide-cel group (median, 2 days) versus cilta-cel group (median, 4 days; P<0.001). The incidence of ICANS was similar, with ICANS of any grade occurring in 19%, respectively. However, severe ICANS grade 3-4 was seen in 7% of the cilta-cel group versus 2% of the ide-cel group. Non-relapse mortality was similar (P=0.52), being 6% in the cilta-cel group versus 5% in the ide-cel group. All 7 deaths without relapse/progression were due to infection in both groups.
Furthermore, we evaluated possible differences in resource utilization. The median length of the hospital stay was 14 days in the ide-cel group versus 17 days in the cilta-cel group (P=0.002). Use of tocilizumab was similar, while use of corticosteroids appeared to be more likely in the cilta-cel group (P=0.04), being used in 35% versus 26% in the ide-cel group.
Last, we evaluated CAR-T dynamics, finding that ide-cel was associated with significantly earlier expansion (P<0.001), peaking at day 7 after infusion. In contrast, cilta-cel expansion peaked at day 14 with significantly increased AUC (P<0.001). CAR-T expansion showed stronger association with ORR and PFS for cilta-cel versus ide-cel (P<0.001). Findings were established with PCR and validated in centers with FACS.
Conclusion Our study provides real-world evidence that cilta-cel was associated with superior outcomes versus ide-cel in triple-class exposed RRMM. Despite similar non-relapse mortality in both groups, different toxicity profiles of cilta-cel must be taken into account in clinical practice.
Disclosures: Gagelmann: BMS: Honoraria; J&J: Honoraria, Other: Travel support. Fenk: Sanofi: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Other: travel expenses; GlaxoSmithKline (GSK): Other: travel expenses; BMS/Celgene: Honoraria, Other: travel accommodation and expenses; Amgen: Honoraria; Pfizer: Honoraria. Holderried: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; GlaxoSmithKline (GSK): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: travel expenses; Janssen: Other: travel expenses; Astellas Pharma: Other: travel expenses; Neovii: Other: travel expenses; Immatics: Other: travel expenses; Sobi: Other: travel expenses. Oliver-Caldés: Janssen: Other: Travel Grants. Vucinic: Amgen: Honoraria, Other: Travel grant; Gilead/Kite, Janssen, BMS Celgene, Novartis: Consultancy, Honoraria. Bärmann: Kite: Membership on an entity's Board of Directors or advisory committees, Other: travel expense; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel expense; Incyte: Other: travel expense; Medac: Other: travel expense; BMS: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees. Ayuk: Medac: Consultancy, Honoraria; Miltenyi Biomedicine: Consultancy, Honoraria; Abbvie: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Honoraria. Platzbecker: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Research Funding; Geron: Consultancy; Curis: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Novartis: Consultancy, Research Funding. Schub: BMS, Janssen: Honoraria. Schmitz: Jazz Pharmaceuticals: Honoraria, Other: Travel/accomodation/expenses; Janssen: Other: Travel/accomodation/expenses; BMS: Ended employment in the past 24 months, Honoraria; Kite/Gilead: Other: Travel/accomodation/expenses; Astellas Pharma: Other: Travel/accomodation/expenses; AbbVie: Other: Travel/accomodation/expenses; Sobi: Honoraria; Incyte: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses; Therakos/Mallinckrodt Pharmaceuticals: Other: Travel/accomodation/expenses. Teichert: Janssen Cilag: Honoraria; Bristol Myers Squibb: Honoraria. Kroeger: DKMS: Research Funding; Alexion, Therakos: Other: Speaker honorarium; BMS: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Neovii, Sanofi, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: speaker honorarium. 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; 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; AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche and Takeda: Honoraria. Merz: Amgen, BMS, Celgene, Gilead, Jannsen, Stemline, SpringWorks and Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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