Clinical Lymphoma, Myeloma & Leukemia, Vol.20, Suppl.1 - September 2020

Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2020 S308 France, 8 Service d’Hématologie et Thérapie Cellulaire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours, France, 9 Department of Clinical Hematology, Centre Hospitalier Versailles, Le Chesnay, France, 10 Unite d’Hematologie et d’Oncologie, Centre Hospitalier Périgueux, Périgueux, France, 11 Department of Oncology Centre Jean Bernard, Institut Inter- regional de Cancerologie, Le Mans, France, 12 Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, 13 Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan, 14 Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan, 15 Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 16 Rocky Mountain Cancer Centers/US Oncology Research, Denver, CO, USA, 17 Department of Hematology, University Hospital Hôtel Dieu, University of Nantes, Nantes, France, 18 Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA, 19 Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA, 20 Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Context: Continuous Rd-based regimens are among the standards of care in the diverse, transplant-ineligible NDMM patient population. An all-oral triplet may be useful for patients who cannot/prefer not to travel to the clinic frequently. Ixazomib, the first oral proteasome inhibitor (PI), has predictable, manageable toxicities, enabling an all-oral PI-Rd regimen for use in this setting. Objective: Compare IRd vs. placebo-Rd in transplant-ineligible NDMM patients. Interventions: Patients were randomized to ixazomib 4 mg (n=351) or placebo (n=354) plus Rd (28-day cycles). After 18 cycles, dexamethasone was discontinued and lower ixazomib and lenalidomide doses were administered until progression or unacceptable toxicity. Main Outcome Measure: Progression-free survival (PFS) - final analysis. Results: In the IRd vs. placebo-Rd arms, the median age was 73 vs. 74 years (43% vs. 44%  75 years), 16% vs. 17% had International Staging System stage III MM, and 38% vs. 41% had high-risk cytogenetics [t(4;14), t(14;16), del(17p), or amp(1q21)]. The median PFS was 35.3 vs. 21.8 months (hazard ratio [HR] 0.830, p=0.073; median follow-up 53.3 vs. 55.8 months). Overall response rates were 82% vs. 80%; depth of response was greater with IRd vs. placebo-Rd (26% vs. 14% complete response [CR], odds ratio [OR] 2.10, p < 0.001; 63% vs. 48%  very good partial response, OR 1.87, p < 0.001). Median time to progression (TTP) was 45.8 vs. 26.8 months (HR 0.738, p=0.008); median overall survival was not reached (HR 0.998, p=0.988; median follow-up 57.8 vs. 58.6 months). In the prespecified high-risk cytogenetics subgroup, the median PFS was 23.8 vs. 18.0 months (HR 0.690, p=0.019). Treatment-emergent adverse events (TEAEs) were mostly grade 1/2. With IRd vs. placebo-Rd, 88% vs. 81% of patients had grade  3 TEAEs, 35% vs. 27% had TEAEs resulting in regimen discontinuation, and 8% vs. 6% of patients died on study, respectively. Conclusions: IRd in NDMM demonstrated a strongly positive trend in PFS, improved TTP and CR rate, and improved the poor PFS associated with high-risk cytogenetics, as seen in the TOURMALINE-MM1 study of IRd in relapsed/refractory MM. Safety was consistent with the well-characterized toxicity profile of ixazomib/IRd. IRd is a feasible treatment option for certain transplant-ineligible patients who could benefit from an all-oral triplet combination. Keywords: elderly, immunomodulatory thalidomide analog, multiple myeloma, MM, proteasome inhibitor MM-350 D ara t umumab ( D ARA) + Lenalid o mide/B o r t e zo mib/ D exame t has o ne (RVd) in African American/Black Pa t ien t s (P t s) wi t h Transplan t-E ligible Newly D iagn o sed Mul t iple Myel o ma (N D MM) : Subgr o up Analysis o f GRIFFIN Ajay K. Nooka 1 *, Jonathan L. Kaufman 1 , Cesar Rodriguez 2 , Andrzej Jakubowiak 3 , Leyla Shune 4 , Ashraf Badros 5 , Ajai Chari 6 , Paul G. Richardson 7 , Huiling Pei 8 , Jon Ukropec 9 , Jessica Vermeulen 10 , Daniela Hoehn 11 , Thomas S. Lin 11 , Peter M. Voorhees 12 1 Winship Cancer Institute, Emory University, Atlanta, GA, USA, 2 Wake Forest University School of Medicine, Winston-Salem, NC, USA, 3 University of Chicago Medical Center, Chicago, IL, USA, 4 Division of Hematologic Malignancies and Cellular Therapeutics (HMCT), University of Kansas Medical Center, Kansas City, MO, USA, 5 University of Maryland, Greenbaum Cancer Center, Baltimore, MD, USA, 6 Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA, 7 Dana-Farber Cancer Institute, Boston, MA, USA, 8 Janssen Research & Development, LLC, Titusville, NJ, USA, 9 Janssen Global Medical Affairs, Horsham, PA, USA, 10 Janssen Research & Development, LLC, Leiden, The Netherlands, 11 Janssen Scientific Affairs, LLC, Horsham, PA, USA, 12 Levine Cancer Institute, Atrium Health, Charlotte, NC, USA Context: To optimize treatment of Black pts with multiple myeloma, a greater understanding of differences in outcomes in Black pts vs. White pts is needed. In GRIFFIN, DARA plus RVd (D-RVd) improved rates and depth of response in autologous stem cell transplant (ASCT)-eligible NDMM pts. Here, we report a subgroup analysis of Black pts from GRIFFIN. Design: Between 2016 and 2018, pts in the United States were randomized 1:1 to RVd ± DARA and received 4 induction cycles, high-dose therapy, ASCT, 2 consolidation cycles, and maintenance with R ± DARA for 24 mo. The pre-specified primary endpoint was stringent complete response (sCR) rate by end of consolidation, which occurred at a median follow-up of 13.5 mo. Results below are based on longer follow- up (22.1 mo). Results: Two hundred seven pts (D-RVd, n=104; RVd, n=103) were randomized; 32 (15%) pts were Black (D-RVd, n=14; RVd, n=18), and 161 (78%) pts were White (D-RVd, n=85; RVd, n=76). Baseline demographics were generally similar between treatment arms in Black andWhite pts. D-RVd vs RVd improved the sCR rate by end of consolidation in Black (10 [71%]; 6 [33%]) and White pts (35 [43%]; 24 [34%]). Including post-consolidation data, sCR with D-RVd vs. RVd was achieved by 12 (86%) and 7 (39%) Black pts and 50 (61%) and 33 (46%) White pts. ORR by end of consolidation was improved for D-RVd vs. RVd in Black pts (14