Type: Oral
Session: 655. Multiple Myeloma: Cellular Therapies: Unleashing Cell Therapies Against Myeloma
Hematology Disease Topics & Pathways:
Chimeric Antigen Receptor (CAR)-T Cell Therapies, Plasma Cell Disorders, Diseases, Biological therapies, Treatment Considerations, Lymphoid Malignancies, Measurable Residual Disease
Methods: Eligibility criteria were previously described. Pts were assigned 1:1 to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd]/daratumumab, pomalidomide, and dexamethasone [DPd]). Pts in the cilta-cel arm underwent apheresis, received bridging therapy (PVd/DPd), and then a single cilta-cel infusion (target dose, 0.75×106 CAR+ viable T cells/kg) 5–7 days (d) after the start of lymphodepletion. PFS was the primary endpoint; ≥CR rate, overall response rate, overall MRD-negativity rate, and OS were key secondary endpoints. MRD was assessed centrally via next-generation sequencing (clonoSEQ v2.0; Adaptive Biotechnologies). MRD was evaluated at d 56 post infusion in the cilta-cel arm; and in both arms at suspected ≥CR and at 6, 12, 18, and 24 mo post infusion (cilta-cel arm) or cycle 1 d 1 (SoC arm), as well as yearly until progression/start of subsequent therapy in pts in ≥CR. Sustained MRD negativity (10−5) was defined as confirmed MRD negativity ≥12 mo apart and without MRD positivity in between. Pts were evaluable for sustained MRD negativity if they achieved MRD negativity and had ≥1 evaluable MRD sample ≥12 mo after the first negative result or progressed/died/started subsequent tx <12 mo after the first negative result.
Results: 419 pts were randomized (intent-to-treat [ITT] set; cilta-cel, n=208; SoC, n=211); 176 pts in the cilta-cel arm received cilta-cel as study tx. As of May 1, 2024, median follow-up for the study was 33.6 mo. At the 10−5 threshold, 145 pts in the cilta-cel arm and 103 in the SoC arm were evaluable for MRD. MRD-negativity rates (10−5) in the ITT set and the MRD-evaluable subset were higher with cilta-cel vs SoC (ITT, 62% vs 18%; MRD evaluable, 89% vs 38%; both P<0.0001). Across subgroups, cilta-cel vs SoC consistently increased overall MRD-negativity rates (10−5). In the ITT set, 48% of the cilta-cel arm achieved MRD negativity (10−5) by d 56, with the MRD-negative rate rising to 60% by 6 mo post cilta-cel infusion. Overall MRD-negativity rates at the 10−6 threshold in the ITT set were higher with cilta-cel vs SoC (57% vs 9%; P<0.0001). In the cilta-cel arm, 119 (57%) pts vs 26 (12%) in the SoC arm achieved overall MRD-negative (10−5) ≥CR (P<0.0001). At the 12-mo MRD assessment, 92 (44%) pts in the cilta-cel arm vs 17 (8%) in the SoC arm (P<0.0001) had MRD-negative (10−5) ≥CR. In pts with MRD-negative (10−5) ≥CR at mo 12, median PFS was not reached (NR; 95% CI, not estimable [NE]–NE) with cilta-cel and 37.8 mo (95% CI, 25.0–NE) with SoC; median OS was NR (95% CI, NE–NE) and NR (95% CI, 37.8 mo–NE), respectively. Sustained MRD-negativity rates (10−5) in the ITT set were 40% in the cilta-cel arm vs 6% in the SoC arm (P<0.0001); among 110 and 26 evaluable pts for sustained MRD, sustained MRD-negativity rates were 75% vs 50% (P=0.0159). Among the 176 pts who received cilta-cel as study tx, overall MRD negativity at 10−5 was achieved by 129 (73%) pts (89% of 145 evaluable pts).
Conclusions: At 33.6-mo median follow-up in CARTITUDE-4, cilta-cel vs SoC significantly increased overall MRD-negativity rates >3-fold in the ITT set, with pts achieving MRD negativity rapidly post cilta-cel. The prognostic value of MRD-negative ≥CR at mo 12 was shown, as median PFS was >3 years in pts with MRD-negative ≥CR at mo 12, regardless of tx. These data further underscore the benefit of cilta-cel, which led to significant >3-fold increases vs SoC in rates of MRD-negative ≥CR at any time and at mo 12, and sustained MRD negativity. Our MRD data demonstrate higher rates of deep and sustained MRD negativity achieved with cilta-cel vs SoC in tx of len-refractory MM as early as first relapse.
Disclosures: Popat: BMS: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Speakers Bureau; Sanofi: Honoraria; GSK: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding, Speakers Bureau. Oriol: Bristol Myers Squibb/Celgene: Honoraria, Speakers Bureau; Pfizer, Amgen, Oncopeptides: Honoraria; Sanofi: Honoraria, Speakers Bureau; GSK: Honoraria, Speakers Bureau; Johnson & Johnson, Janssen: Honoraria, Speakers Bureau. Karlin: AbbVie, Amgen, Celgene, Janssen, Sanofi, Takeda: Honoraria; Amgen, Celgene, GSK, Janssen, and Takeda: Other: Advisory role. Avivi Mazza: AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Roeloffzen: Abbvie: Other: Travel expenses; BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Other: Travel expenses, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau. Lipe: Janssen, karyopharm, bms, Sanofi, Pfizer, and abbvie: Consultancy, Honoraria; Janssen and amgen: Research Funding. Spencer: F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Research Funding. Li: Janssen R&D: Current Employment, Current equity holder in publicly-traded company. Slaughter: Johnson & Johnson Innovative Medicine: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Lonardi: J&J Innovative Medicine: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Benachour: Johnson & Johnson: Current Employment. Ghosh: Janssen: Current Employment, Current equity holder in publicly-traded company. Vogel: Janssen: Current Employment, Current equity holder in publicly-traded company. Lendvai: Johnson and Johnson Innovative Medicine: Current Employment, Current equity holder in publicly-traded company. Lengil: Janssen: Current Employment, Current equity holder in publicly-traded company. Patel: Legend Biotech, GSK, Freeline, BMS (spouse), AbbVie (spouse): Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Costa Filho: Legend Biotech: Current Employment. Florendo: Legend Biotech: Current Employment. Lin: Legend: Consultancy; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Research Funding; NexImmune: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; Janssen: Consultancy, Research Funding; Genentech: Consultancy.
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