denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Type: Oral
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Optimizing Therapy in Newly Diagnosed Myeloma and Beyond
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Clinical Research, Plasma Cell Disorders, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy, Study Population, Human, Measurable Residual Disease
Methods: Eligible pts with NDMM were 18-79 yrs of age, in very good partial response or better (≥VGPR) and positive for minimal residual disease (MRD [10–5]; NGS) following ASCT, anti-CD38 naïve, received ≥4 induction cycles, and enrolled within 12 months of start of induction therapy and 6 months of ASCT. Pts received 28-day cycles of R maintenance (10mg PO D1-28 [after C3, 15mg PO, if tolerated]) ± subcutaneous DARA (DARA SC; 1,800mg QW C1-2, Q2W C3-6, Q4W C7+) for up to 36 cycles or until disease progression, unacceptable toxicity, or withdrawal. Pts benefiting from DARA and/or R could continue treatment after the end of the study treatment period, per the investigator’s discretion. The primary endpoint was MRD-negative (10–5) conversion rate by 12 months from start of maintenance therapy.
Results: 200 pts were randomized (D-R, n=99; R, n=101); subgroups had similar numbers of pts per arm: <65 years (n=61; n=61), ≥65 yrs (n=38; n=40), Black (n=20; n=24), White (n=67; n=68), and at diagnosis: ISS stage III disease (n=23; n=23), normal (n=63; n=66) and high cytogenetic risk (n=22; n=15) per the standard definition, and normal (n=52; n=53) and high cytogenetic risk (n=32; n=30) per the revised definition. The MRD-negative (10–5) conversion rate by 12 months was consistently higher for D-R vs R across subgroups: <65 yrs (49.2% vs 19.7%; odds ratio [OR], 3.95; 95% CI, 1.76-8.85), ≥65 yrs (52.6% vs 17.5%; OR, 5.24; 95% CI, 1.86-14.74); Black (60.0% vs 16.7%; OR, 7.50; 95% CI, 1.85-30.34); White (46.3% vs 20.6%; OR, 3.32; 95% CI, 1.55-7.10); ISS stage III (65.2% vs 13.0%; OR, 12.50; 95% CI, 2.83-55.25); normal (55.6% vs 21.2%; OR, 4.64; 95% CI, 2.15-10.04) and high cytogenetic risk per the standard definition (31.8% vs 6.7%; OR, 6.53; 95% CI, 0.71-60.05); and normal (53.8% vs 22.6%; OR, 3.99; 95% CI, 1.72-9.26) and high cytogenetic risk per the revised definition (43.8% vs 13.3%; OR, 5.06; 95% CI, 1.43-17.88). At 32.3 months of median follow-up, PFS hazard ratio (HR) point estimates among subgroups consistently favored D-R vs R: <65 yrs (HR, 0.51; 95% CI, 0.22-1.18), ≥65 yrs (HR, 0.71; 95% CI, 0.30-1.67); Black (HR, 0.66; 95% CI, 0.16-2.75); White (HR, 0.56; 95% CI, 0.28-1.12); ISS stage III (HR, 0.26; 95% CI, 0.08-0.85); normal (HR, 0.59; 95% CI, 0.23-1.49) and high cytogenetic risk per the standard definition (HR, 0.60; 95% CI, 0.21-1.70); and normal (HR, 0.69; 95% CI, 0.24-1.95) and high cytogenetic risk per the revised definition (HR, 0.53; 95% CI, 0.21-1.31). Additional data in other high-risk subgroups, including 1q21 abnormalities, will be presented.
The incidence of grade 3/4 TEAEs was higher for D-R vs R for both Black (D-R, 75.0% [15/20]; R, 66.7% [16/24]) and White (76.6% [49/64]; 70.8% [46/65]) pts. Grade 3/4 TEAEs occurred more frequently for D-R vs R in pts <65 yrs (D-R, 76.3% [45/59]; R, 63.8% [37/58]), and were similar for D-R vs R in pts ≥65 yrs (70.3% [26/37]; 72.5% [29/40]). Grade 3/4 infection rates for D-R vs R among subgroups were: Black (D-R, 20% [4/20]; R, 20.8% [5/24]); White (20.3% [13/64]; 12.3% [8/65]); <65 yrs (18.6% [11/59]; 10.3% [6/58]); ≥65 yrs (18.9% [7/37]; 17.5% [7/40]).
Conclusion: This post hoc analysis of AURIGA showed that addition of DARA to R maintenance demonstrated improvement across clinically relevant subgroups in MRD-negative conversion rate by 12 months from the start of maintenance as well as PFS. Grade 3/4 TEAEs were higher for D-R vs R in Black and White pts, as well as those <65 yrs. These results demonstrate the benefit of adding DARA to R maintenance in clinically relevant subgroups of anti-CD38 naïve pts with NDMM who were positive for MRD post-ASCT.
Disclosures: Foster: Janssen: Other: Advisory Board; BMS: Other: Advisory board; ASH Reimbursement Subcommittee member: Other: Leadership role; GABA Therapeutics: Current holder of stock options in a privately-held company; EVMS 12th Winter Hematology Conference Targeted Oncology Virtual Roundtable Hematologic Malignancies Update from NEJM Group: Honoraria; RNA Advisors, FosterRosenblatt: Consultancy. Anderson: Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Chung: Abbvie: Research Funding; CarsGen Therapeutics: Research Funding; Cellectis: Research Funding; Merck: Research Funding; Caelum Biosciences: Research Funding; Johnson & Johnson Innovative Medicine: Membership on an entity's Board of Directors or advisory committees, Other: travel reimbursement, Research Funding; K36 Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Genentech: Research Funding. Cowan: Sebia, Janssen, BMS, Sanofi, HopeAI, Adaptive Biotechnologies, Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie, Adaptive Biotechnologies, Janssen, BMS, Juno/Celgene, Sanofi, Regeneron, IGM BIosciences, Nektar, Harpoon, Caelum: Research Funding. Costello: BMS, Janssen, Karyopharm, Kite, Genentech, Pfizer: Honoraria; BMS; Harpoon; Janssen; Pfizer; Poseida; and Takeda: Research Funding; BMS; Genentech; Janssen; Karyopharm; Kite; and Pfizer: Consultancy. Larson: Ionis: Other: Clinical trial; Sanofi: Other: Clinical trial; Regeneron: Other: Clinical trial; BMS: Other: Clinical trial; Pfizer: Other: Clinical trial; Bioline: Other: Clinical trial; Allogene: Other: Clinical trial; Janssen: Research Funding; Immpact bio: Other: Clinical trial; TORL Biotherapeutics: Current holder of stock options in a privately-held company. Sborov: Amgen, Celgene, and Janssen, GlaxoSmithKline, Abbvie, Pfizer, Astra Zeneca, Bioline, Sanofi, and Genentech: Consultancy; Celgene: Honoraria; Paraxel: Other: Independent review committee; Pfizer: Research Funding; Janssen, Karyopharm: Membership on an entity's Board of Directors or advisory committees. Shain: Takeda: Consultancy; Karyopharm: Research Funding; Abbvie: Research Funding; Amgen: Research Funding; Sanofi: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Glaxo Smith Kline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm, Janssen, Adaptive Biotechnologies, GlaxoSmithKline, BMS, Sanofi, and Regeneron: Honoraria; Adaptive Biotech: Consultancy. Silbermann: Sanofi-Aventis, Janssen Oncology, and Oncopeptides: Consultancy; Sanofi: Research Funding. Voorhees: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; GSK: Consultancy, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Lava Therapeutics: Consultancy. Krevvata: Janssen: Current Employment, Current holder of stock options in a privately-held company. Pei: Johnson & Johnson Innovative Medicine: Current Employment, Current equity holder in publicly-traded company. Patel: Janssen Scientific Affairs, LLC, a Johnson & Johnson company: Current Employment, Current equity holder in publicly-traded company. Khare: Johnson & Johnson Innovative Medicine: Current Employment, Current equity holder in publicly-traded company. Cortoos: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Carson: Janssen: Current Employment, Current holder of stock options in a privately-held company. Lin: Johnson & Johnson Innovative Medicine: Current Employment, Current equity holder in publicly-traded company; GlaxoSmithKline: Current equity holder in publicly-traded company. Badros: GSK: Research Funding; BMS: Research Funding; BeiGene: Research Funding; Roche: Research Funding; Janssen: Research Funding.
OffLabel Disclosure: Daratumumab is currently approved in combination with standard regimens for the treatment of patients with transplant-eligible newly diagnosed multiple myeloma, but it is not yet approved in combination with lenalidomide for maintenance therapy for patients with transplant-eligible newly diagnosed multiple myeloma.