Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Biological therapies, clinical trials, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Plasma Cell Disorders, Clinical Research, Diseases, Therapies, Lymphoid Malignancies
Study Design and Methods: Eligible patients are aged ≥18 years with NDMM per International Myeloma Working Group diagnostic criteria, have measurable disease at screening, and have high-dose therapy and ASCT as part of their intended initial treatment plan. Exclusion criteria are patients who have received any prior therapy for MM or smoldering myeloma (except a short course of corticosteroids). After giving informed consent, patients are randomized 1:1 into 2 treatment arms (target recruitment: N=750). In the cilta-cel arm, patients will undergo apheresis before receiving 6 cycles of DVRd induction. After induction, patients will receive lymphodepletion (intravenous cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days), followed by a single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) 5–7 days later. After the cilta-cel infusion, patients will receive lenalidomide post CAR-T therapy for 2 years (or longer, at investigator discretion). In the control arm, patients will receive 4 cycles of DVRd induction, followed by ASCT and 2 cycles of DVRd consolidation. Patients will then receive lenalidomide maintenance for 2 years (or longer at investigator discretion). The dual primary endpoints are progression-free survival (PFS) and minimal residual disease (MRD)-negative CR sustained for ≥12 months, with MRD status determined by next-generation sequencing at a sensitivity of at least 10-5. Secondary endpoints include ORR, ≥CR rate, overall MRD-negative CR rate, time to subsequent therapy, PFS on next-line therapy, overall survival, adverse events, pharmacokinetic/pharmacodynamic markers, and changes in health-related quality of life. Exploratory correlative biomarker analyses will also be performed. Enrollment opens in September 2022, with anticipated primary completion in June 2026. This study will investigate the efficacy and safety of a cellular therapy approach with cilta-cel versus standard of care ASCT in patients with NDMM who are transplant eligible.
Disclosures: Boccadoro: Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Research Funding. San-Miguel: Abbvie, Amgen, BMS, Celgene, GSK, Haemalogix, Janssen-Cilag, Karyopharm, MSD, Novartis, Takeda, Regeneron, Roche, Sanofi, and SecuraBio: Consultancy, Other: Advisory Board. Suzuki: Takeda, ONO, Amgen, Novartis, Sanofi, Bristol Myers Squibb, AbbVie, and Janssen: Honoraria; Amgen, Takeda, and Bristol Myers Squibb: Consultancy; Bristol Myers Squibb: Research Funding. Krishnan: Pfizer: Consultancy; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Research Funding; Sanofi: Consultancy; AstraZeneca: Consultancy; Takeda, GSK, BMS: Speakers Bureau; Artiva: Consultancy; Janssen: Consultancy, Research Funding; BMS, Janssen, Adaptive, GSK, AbbVie, Regeneron, Sanofi, AstraZeneca: Consultancy; Sutro SAB: Speakers Bureau; Regeneron: Consultancy; BMS: Current equity holder in publicly-traded company; Adaptive: Consultancy; Bristol Myers Squibb: Consultancy, Other: Stock Ownership (not including stocks owned in a managed portfolio), Speakers Bureau; Sutro: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau. Van De Donk: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Cook: Takeda, BMS, Amgen, Roche, Janssen, Sanofi, Karyopharm, Pfizer: Consultancy; Takeda, BMS: Research Funding; Takeda, BMS, Amgen, Janssen, Sanofi: Speakers Bureau. Jakubowiak: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Madduri: BMS, Takeda, GSK, Kinevant, Legend, Sanofi, Celgene: Consultancy; Amgen, Allogene, BMS, Celgene: Research Funding; Janssen: Current Employment. Afifi: Janssen Research & Development: Current Employment. Stevens: Janssen Research & Development: Current Employment. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Deraedt: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Kuppens: Janssen Research & Development: Current Employment. Pacaud: Legend Biotech USA: Current Employment. Florendo: Legend Biotech: Current Employment. Broijl: Janssen: Other: Advisory boards/honoraria; Sanofi: Other: Advisory boards/honoraria; Amgen: Other: Advisory boards/honoraria; Bristol Myers Squibb: Other: Advisory boards/honoraria. Gay: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Mina: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy. Rasche: GSK: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau: AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Sanofi: Honoraria. Mateos: Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides, Seagen: Honoraria. Einsele: BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Other: travel grants. Sonneveld: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding.