Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
Research, Biological therapies, clinical trials, adult, Clinical Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy, Human, Study Population, Minimal Residual Disease
Methods: In GRIFFIN, pts with transplant-eligible NDMM were randomized 1:1 to D-RVd or RVd. All pts received 4 D-RVd/RVd induction cycles, ASCT, 2 D-RVd/RVd consolidation cycles, and maintenance with lenalidomide (R) ± DARA for 24 months. All pts received 21-day cycles of R (25 mg PO on Days [D] 1-14), bortezomib (1.3 mg/m2 SC on D1, 4, 8, 11), and dexamethasone (40 mg PO QW) ± DARA (16 mg/kg IV QW in Cycles 1-4 and D1 in Cycles 5-6). During maintenance (Cycles 7-32; 28-day cycles), pts received R (10 mg PO on Days 1-21; if tolerated, 15 mg in Cycles 10+) ± DARA (16 mg/kg IV Q8W/Q4W or 1800 mg SC Q4W per protocol amendments). The primary endpoint was the sCR rate by end of consolidation.
Results: 207 pts were randomized (D-RVd, n = 104; RVd, n = 103); each subgroup had a similar number of pts per arm: ≥65 years (n = 28; n = 28), ISS stage III disease (n = 14; n = 14), high cytogenetic risk (n = 16; n = 14), revised high cytogenetic risk (n = 42; n = 37), gain/amp1q (n = 34; n = 28), 1 HRCA (n = 32; n = 29), gain/amp1q plus 1 HRCA (n = 9; n = 6), and ≥2 HRCA (n = 10; n = 8). Outcomes for pts with baseline extramedullary plasmacytomas (D-RVd, n = 1; RVd, n = 2) were explored but not included due to small pt numbers. Among response-evaluable pts, the rate of sCR at the end of maintenance therapy was numerically higher for D-RVd versus RVd among pts with age ≥65 years (63.0% vs 40.7%; OR, 2.47; 95% CI, 0.83-7.39), high cytogenetic risk (50.0% vs 38.5%; OR, 1.60; 95% CI, 0.36-7.07), gain/amp1q plus 1 HRCA (55.6% vs 33.3%; OR, 2.50; 95% CI; 0.29-21.40), and ≥2 HRCA (50.0% vs 37.5%; OR, 1.67; 95% CI, 0.25-11.07), but similar for D-RVd and RVd pts with ISS stage III disease (64.3% vs 61.5%; OR, 1.13; 95% CI, 0.24-5.37), revised high cytogenetic risk (56.1% vs 55.6%; OR, 1.02; 95% CI, 0.42-2.52), gain/amp1q (57.6% vs 57.1%; OR, 1.02; 95% CI, 0.37-2.82), and 1 HRCA (58.1% vs 60.7%; OR, 0.90; 95% CI, 0.32-2.54). MRD-negativity (10–5) rates at the end of maintenance favored D-RVd over RVd across all subgroups (Figure A). At 49.6 months of median follow-up, PFS rates among subgroups favored D-RVd over RVd except for pts with ≥2 HRCA (Figure B).
In pts ≥65 years, grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 88.9% of D-RVd and 77.8% of RVd pts; the most common grade 3/4 TEAEs (≥20%) were neutropenia (D-RVd, 37.0%; RVd, 29.6%) and lymphopenia (25.9%; 11.1%). TEAEs led to study treatment discontinuation in 37.0% of D-RVd and 25.9% of RVd pts. In pts ≥65 years, death as outcome of a TEAE occurred in 1 D-RVd pt (pneumonia; unrelated to study treatment).
Conclusions: In this final analysis of GRIFFIN by clinically relevant subgroups, addition of DARA to RVd induction/consolidation and R maintenance, with ASCT, was associated with higher MRD-negativity (10–5) rates for all subgroups and PFS estimates favored all high-risk groups except pts with ≥2 HRCA. Among pts ≥65 years, the rates of grade 3/4 TEAEs and TEAEs leading to study treatment discontinuation were slightly higher for the D-RVd group, although only 1 pt died due to a TEAE unrelated to study treatment. Results of this subgroup analysis support the use of DARA in transplant-eligible pts with NDMM among both clinically and cytogenetic high-risk subgroups, although larger studies are needed, especially in pts with ≥2 HRCA.
Disclosures: Kaufman: AbbVie: Other: Member of steering committee; AbbVie, Genentech, and Bristol Myers Squibb: Consultancy; Incyte: Other: Member of data safety monitoring committee . Laubach: Lignancies: Honoraria. Sborov: GlaxoSmithKline, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Skyline Dx, Janssen, AbbVie, Sanofi: Consultancy; BMS: Consultancy. Reeves: Incyte, BMS, PharmaEssentia, CTI Biopharma: Honoraria; Hemostasis & Thrombosis Research Society Mentored Research Award sponsored by CSL Behring: Research Funding. Rodriguez: Janssen, BMS, Takeda, AbbVie, karyopharm, Artiva: Consultancy, Speakers Bureau. Silbermann: Sanofi-Aventis: 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; Pfizer: Membership on an entity's Board of Directors or advisory committees. Megala Costa: Janssen: Consultancy, Honoraria, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; AbbVie: Research Funding; Genentech: Research Funding. Anderson: Celgene: 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; Karyopharm: 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; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: 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; Prothena: 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; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah: GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm, Oncopeptides,: Consultancy; AstraZeneca: Current Employment, Current equity holder in publicly-traded company; Aztra Zeneca: Current Employment, Other: stock ownership; Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar, Precision Biosciences: Research Funding. Bumma: Sanofi, Genzyme: Other: Ad Board, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Ad Board; Amgen: Consultancy, Speakers Bureau. Holstein: Genentech: Consultancy; Janssen: Consultancy, Research Funding; Secura Bio: Consultancy; Oncopeptides: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Sanofi: Consultancy. Costello: BMS, Takeda, Janssen, Pfizer: Consultancy, Honoraria, Research Funding. Jakubowiak: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Wildes: Janssen: Consultancy; Sanofi: Consultancy; Seattle Genetics: Consultancy; Carevive: Consultancy. Orlowski: Abbvie, BioTheryX, Inc., Bristol-Myers Squibb, Janssen Biotech, Karyopharm Therapeutics, Inc., Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda Pharmaceutic: Honoraria, Membership on an entity's Board of Directors or advisory committees; CARsgen Therapeutics, Celgene/Bristol Myers Squibb, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Asylia Therapeutics, Inc., BioTheryX, Inc., Heidelberg Pharma, Inc.: Research Funding; Asylia Therapeutics, Inc.: Current equity holder in private company. Shain: Janssen,BMS: Other: PI of clinical trials; AbbVie, Karyopharm: Research Funding; GSK, Janssen and BMS and speaker’s bureau for GSK, BMS, Sanofi, Karyopharm, Takeda, Janssen, Adaptive and Amgen: Other: Advisory Committee; Bristol Myers Squibb (BMS), Janssen, GlaxoSmithKline (GSK), Adaptive, Sanofi, and Takeda, and Amgen: Honoraria. Cowan: Secura bio: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; EUSA: Consultancy; Allogene: Consultancy; AbbVie: Consultancy, Research Funding; Nektar: Research Funding; BMS: Consultancy, Research Funding; Sanofi-Aventis: Research Funding; Harpoon: Research Funding; Janssen: Consultancy, Research Funding. Pei: Janssen: Current Employment, Current equity holder in publicly-traded company. Cortoos: Janssen: Current Employment, Current equity holder in publicly-traded company. Patel: Companies of Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Lin: Janssen: Current Employment, Current holder of stock options in a privately-held company. Richardson: Sanofi: Consultancy; Regeneron: Consultancy; AstraZeneca: Consultancy; GlaxoSmithKline: Consultancy; Protocol Intelligence: Consultancy; Abbvie: Consultancy; Secura Bio: Consultancy; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding. Usmani: AbbVie, Amgen, BMS, Celgene, EdoPharma, Genentech, Gilead, GSK, Janssen Pharmaceuticals, Oncopeptides, Sanofi, Seagen Inc., formerly Seattle Genetics, Inc., Secura Bio, Inc., SkylineDX, Takeda, TeneoBio , Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen: Research Funding; Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen Pharmaceuticals, Merck, Pharmacyclics, Sanofi, Seagen Inc., formerly Seattle Genetics, Inc., SkylineDX, Takeda: Consultancy; Amgen, BMS, Janssen Pharmaceuticals, Sanofi: Speakers Bureau. Voorhees: Abbvie, Amgen, BMS, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Sanofi, SecuraBio: Consultancy, Honoraria.
OffLabel Disclosure: The specific regimen combination is not yet approved, but individual components are.
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