Safety and efficacy of four drug regimens in newly diagnosed multiple myeloma: Systematic review.

person Udhayvir Singh Grewal Cleveland Clinic, Cleveland, OH info_outline Udhayvir Singh Grewal, Rajshekhar Chakraborty, Fazal I Raziq, Afia Ashraf, Ammara Majeed, Vikas Kapoor, Anne Hubben, Rujul Parikh, Midhat Lakhani, Azka Latif, Atlantis Dawn Russ, Faiz Anwer

Authors person Udhayvir Singh Grewal Cleveland Clinic, Cleveland, OH info_outline Udhayvir Singh Grewal, Rajshekhar Chakraborty, Fazal I Raziq, Afia Ashraf, Ammara Majeed, Vikas Kapoor, Anne Hubben, Rujul Parikh, Midhat Lakhani, Azka Latif, Atlantis Dawn Russ, Faiz Anwer Organizations Cleveland Clinic, Cleveland, OH, Michigan State University, East Lansing, MI, Anne Arundel Medical Center, Annapolis, MD, Suquino Inc, Sunnyvale, CA, University of Arizona, Tucson, AZ, Cleveland Clinic Foundation, Cleveland, OH, Dow Medical College, Pakistan, Karachi, Pakistan, University of Arizona College of Medicine Internal Medicine, Tucson, AZ, Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland, OH Abstract Disclosures Research Funding Other Background: To improve outcomes, multiple agents with varied mechanisms of action targeting different multiple myeloma (MM) clones are needed. Methods: Systematic review of ongoing phase I-III clinical trials in newly diagnosed multiple myeloma (NDMM) was performed, (PRISMA guidelines) using 5 databases. Results: 8 trials n = 1,990 patients included (Table 1). We evaluated the efficacy of following four drug combinations Isatuximab (Isa), bortezomib (V), lenalidomide (R)dexamethasone (d) (Isa-VRd) Daratumumab (Dara) plus V, Melphalan (M) and Prednisone (P) (Dara-VMP) vs VMP Dara-VRd vs VRd Carfilzomib (K), Cyclophosphamide (C), R, Dexamethasone (KCRD) vs an immunomodulatory agent containing triplet (CTD/CRD) Dara with Ixazomib (I), R,d (Dara- IRd) Dara, Cyclophosphamide (Cy), V,d (Dara-CyBord) Elotuzumab (Elo) VRd Dara with K,R,d (Dara- KRd) For transplant-eligible patients, Dara-VRd demonstrated the best treatment response (VGPR = 100%, CR rate = 63% and 15 months PFS = 94%). Dara-VMP (ORR = 90.9%,VGPR+ = 72.9%, mPFS at 27. 8 m = NR) and Isa+VRd (ORR = 93%, VGPR = 71.43%, 7.5 m PFS = 100%) were associated with improvement in OR in transplant ineligible patients. Dara-KRd showed excellent efficacy (ORR = 100%, ≥VGPR = 86%) with 100% 6 m PFS. Conclusions: Four-drug regimens have improved efficacy (higher ORR, deeper response, higher proportion of MRD negativity and higher ≥VGPR responses) compared to three-drug regimens in NDMM, with a comparable incidence of toxicities. Longer follow-up is needed. Study No. of patients Phase of study Efficacy Data Safety Data Dara-VMP vs VMP Dimopoulos MA, 2018 706 Phase III ORR = 90.9% sCR = 22.3% VGPR = 27.7% PR = 18.0% ≥VGPR = 72.9% CR+ = 45.1% Median PFS (at 27.8 months) = NR Grade 3 or 4 TEAEs = 23.7% KCRD vs CTD/CRD Jackson 2018 1056 Phase III CR = 17.7% nCR = 38.6% VGPR = 26% PR = 8.2% PFS = NR Grade 3+ neutropenia = 16.6% Grade 3+ thrombocytopenia = 8.4% Dara-IRD Kumar 2018 40 Phase II CR = 11% VGPR = 47% Median 5 month PFS = 100% ORR = 95% Grade ≥3 AEs = 42% Dara-VRD vs VRD Voorhees 2018 16 Phase II ≥VGPR = 100% CR or sCR = 63% MRD negativity = 50% 15 months PFS = 94% Grade 3 or 4 TEAEs = 88% Dara-CVD Yimer 2018 87 NDMM (101 total) Phase II ≥VGPR = 56% CR = 9% ORR = 81% 12 month PFS = 87% OS = 99% Grade ≥3 AEs = 56% Elotozumab-VRd Laubauch 2017 41 Phase II ORR = 100% CR = 24% VGPR = 47% PR = 29% ≥VGPR = 71% Grade 3+ thrombocytopenia = 15% Dara-KRd Jakubowiak 2017 22 Phase I ORR = 100% CR = 5% ≥VGPR = 86% 6 months PFS = 100% Grade 3 or 4 TEAEs = 82% Isatuximab-VRd (Ocio 2018 22 Phase I ORR = 93% MRD negativity = 38.5% sCR = 7.14% VGPR = 71.43% CR = 7.14% 7.5 months PFS = 100% Grade ≥3 AEs = 46%