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4560 An End-of-Study Subgroup Analysis of Black Patients from the Phase 2 Griffin Study of Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM)

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Research, clinical trials, adult, Clinical Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy, Study Population, Human, Minimal Residual Disease
Monday, December 12, 2022, 6:00 PM-8:00 PM

Ajay K. Nooka, MD, MPH, FACP1, Jonathan L. Kaufman, MD2, Cesar Rodriguez, MD3*, Andrzej Jakubowiak, MD, PhD4, Yvonne A. Efebera, MD, MPH5, Brandi Reeves, MD6, Tanya M. Wildes, MD7*, Sarah A. Holstein, MD, PhD7, Larry D. Anderson Jr., MD, PhD8, Ashraf Z. Badros, MD9, Leyla O. Shune, MD10, Ajai Chari11*, Huiling Pei, PhD12*, Annelore Cortoos, MD13*, Sharmila Patel, PhD13*, Thomas S. Lin, MD, PhD13, Paul G. Richardson, MD14, Saad Usmani, MD15 and Peter M. Voorhees, MD16*

1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
2Winship Cancer Institute of Emory University Hospital, Atlanta, GA
3Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
4University of Chicago Medical Center, Chicago, IL
5OhioHealth, Columbus, OH
6University of North Carolina at Chapel Hill, Chapel Hill, NC
7Division of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
8Myeloma, Waldenstrom’s and Amyloidosis Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
9Greenbaum Cancer Center, University of Maryland, Baltimore, MD
10Division of Hematologic Malignancies and Cellular Therapeutics (HMCT), University of Kansas Medical Center, Kansas City, KS
11Icahn School of Medicine at Mount Sinai, New York, NY
12Janssen Research & Development, LLC, Titusville, NJ
13Janssen Scientific Affairs, LLC, Horsham, PA
14Dana-farber/Boston Children's Cancer and Blood Disorders Ctr, Boston, MA
15Memorial Sloan Kettering Cancer Center, New York, NY
16Levine Cancer Institute, Atrium Health Wake Forest Baptist, Charlotte, NC

Introduction: Optimal treatment remains to be defined for Black patients with transplant-eligible NDMM. The primary analysis of the randomized phase 2 GRIFFIN study (NCT02874742) demonstrated that frontline therapy of DARA plus RVd (D-RVd) had superior clinical benefit versus RVd in the overall study population (Voorhees PM, et al. Blood. 2020). A post hoc subgroup analysis of Black patients in the GRIFFIN study was previously reported; this analysis occurred after 1 year of maintenance therapy with lenalidomide (R) ± DARA (median follow-up, 27.4 mo) and showed that D-RVd improved depth of response versus RVd among Black patients, with a comparable safety profile to White patients (Nooka AK, et al. Blood Cancer J. 2022). Here, we present the end-of-study final analysis of GRIFFIN by race (median follow-up, 49.6 mo), which occurred after all patients completed study therapy and 1 year of long-term follow-up, discontinued, or withdrew.

Methods: Patients with transplant-eligible NDMM were randomized 1:1 to receive D-RVd or RVd. All patients received 4 D-RVd/RVd induction cycles, autologous stem cell transplant (ASCT), 2 D-RVd/RVd consolidation cycles, and up to 2 years of maintenance with R ± DARA. During induction/consolidation, all patients received 21-day cycles of R (25 mg PO on Days [D] 1-14), V (1.3 mg/m2 SC on D1, 4, 8, 11), and d (40 mg PO QW) ± DARA (16 mg/kg IV QW in Cycles 1-4 and D1 in Cycles 5-6). During maintenance (28-day cycles), patients received R (10 mg PO on D1-21; if tolerated, 15 mg Cycles 10+) ± DARA (16 mg/kg IV Q8W/Q4W or 1800 mg SC Q4W per protocol amendments). After completion of study therapy, patients could continue on R maintenance therapy per local standard of care. The primary endpoint was sCR rate post-ASCT consolidation treatment.

Results: Of 207 randomized patients (D-RVd, n = 104; RVd, n = 103), 32 (15%) were Black (D-RVd, n = 14; RVd, n = 18) and 161 (78%) were White (D-RVd, n = 85; RVd, n = 76). Baseline characteristics were generally similar between Black and White patients. sCR rates by the end of maintenance were higher for D-RVd versus RVd in Black (93% vs 39%, P = 0.0021) and White (65% vs 50%, P = 0.0589) patients (Figure A). MRD-negativity (10–5) rates by the end of maintenance were higher for D-RVd versus RVd for Black (64% vs 22%, P = 0.0293) and White (66% vs 32%, P < 0.0001) patients (Figure B). With median overall follow-up of 49.6 months, D-RVd reduced the risk of disease progression or death by 61% in Black patients (HR, 0.39; 95% CI, 0.07-2.24, P = 0.2767) and 53% in White patients (HR, 0.47; 95% CI, 0.19-1.18, P = 0.1003), compared with RVd. For Black patients, estimated 48-month PFS rates were 79% for D-RVd and 65% for RVd; among White patients, estimated 48-month PFS rates were 89% for D-RVd and 74% for RVd. There were no deaths among Black patients, and there were 12 deaths among White patients (D-RVd, n = 6; RVd, n = 6).

The most common (≥30%) grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (Black: D-RVd, 50% vs RVd, 22%; White: D-RVd, 47% vs RVd, 18%) and lymphopenia (29% vs 39%; 23% vs 16%). Serious adverse events occurred more frequently in the RVd group in Black patients (D-RVd, 43% vs RVd, 56%) and were similar for both treatment arms in White patients (D-RVd, 47% vs RVd, 49%). Infusion-related reactions occurred in 29% of Black patients and 53% of White patients who received D-RVd. TEAEs that led to study treatment discontinuation occurred in 64% and 39% of Black D-RVd and RVd patients, respectively, and 29% and 26% of White D-RVd and RVd patients, respectively. Peripheral neuropathy was seen more frequently in the RVd group both in Black (D-RVd, 57% vs RVd, 67%) and White patients (D-RVd, 64% vs RVd, 78%); most events were grade 1/2. No deaths occurred due to TEAEs among Black patients, and 1 White patient in the D-RVd group had a death due to a TEAE (pneumonia).

Conclusions: In this final end-of study analysis of GRIFFIN by race, the frontline therapy of DARA plus RVd for induction/consolidation and DARA plus R maintenance continued to demonstrate clinical benefit among Black patients. However, 48-month PFS rates for both D-RVd and RVd were lower in Black patients than in White patients, and this may be attributed to the higher rates of study treatment discontinuation following TEAEs in Black patients. More investigations of treatment delivery and TEAE management in Black patients compared to White patients are warranted.

Disclosures: Nooka: Bristol-Myers Squibb, Janssen, Takeda, Amgen, Adaptive, GlaxoSmithKline, Sanofi, Oncopeptides, Karyophram, SecureBio, and BeyondSprings: Consultancy, Honoraria. Kaufman: AbbVie, Genentech, and Bristol Myers Squibb: Consultancy; AbbVie: Other: Member of steering committee; Incyte: Other: Member of data safety monitoring committee . Rodriguez: Janssen, BMS, Takeda, AbbVie, karyopharm, Artiva: Consultancy, Speakers Bureau. Jakubowiak: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Efebera: Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; BMS: Research Funding; Pfizer: Honoraria; GSK: Honoraria; Sanofi: Honoraria. Reeves: Incyte, BMS, PharmaEssentia, CTI Biopharma: Honoraria; Hemostasis & Thrombosis Research Society Mentored Research Award sponsored by CSL Behring: Research Funding. Wildes: Carevive: Consultancy; Sanofi: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy. Holstein: Secura Bio: Consultancy; Genentech: Consultancy; Takeda: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding. Anderson: Celgene: 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; 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; Pharmacyclics: 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; Karyopharm: 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; GSK: 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. Badros: Amgen: Consultancy; GSK, BMS: 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: Regeneron: Consultancy; AstraZeneca: Consultancy; Protocol Intelligence: Consultancy; Abbvie: Consultancy; GlaxoSmithKline: Consultancy; Secura Bio: Consultancy; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Sanofi: Consultancy; 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.

*signifies non-member of ASH