Recent updates on three drug combination regimen for relapsed refractory multiple myeloma.

person Tabinda Saleem UPMC Pinnacle, Harrisburg, PA info_outline Tabinda Saleem, Abdul Rafae, Joshua Jonathan Christy, Kiran Kuriakose, Mustafa Nadeem Malik, Emad Kandah, Hafiz Qurashi, Rabia Ali, Faiz Anwer

Authors person Tabinda Saleem UPMC Pinnacle, Harrisburg, PA info_outline Tabinda Saleem, Abdul Rafae, Joshua Jonathan Christy, Kiran Kuriakose, Mustafa Nadeem Malik, Emad Kandah, Hafiz Qurashi, Rabia Ali, Faiz Anwer Organizations UPMC Pinnacle, Harrisburg, PA, McLaren Flint Michigan State University, Flint, MI, Internal Medicine, McLaren Flint- Michigan State University, Flint, MI, UPMC Mckeesport, Pittsburg, PA, University of Arizona, Department of Internal Medicine, Tucson, AZ, UPMC Pinnacle, Harrisburgh, PA, Rawalpindi Medical University, Rawalpindi, Pakistan, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH Abstract Disclosures Research Funding No funding received None Background: Two drug regimens comprising proteasome inhibitors, immunomodulatory agents, or a monoclonal antibody are the standard of care for multiple myeloma. However, due to the increased relapse incidence, multiple different combination therapies are under study to treat relapsed and refractory multiple myeloma (RRMM). Methods: A comprehensive data search was done across various data sets, including PubMed, Cochrane, and Embase, using MeSH terms and keywords to include all phase III clinical trials involving three-drug regimens in the last five years. Results: We report eleven clinical trials evaluating three-drug combination regimens vs. two-drug regimens for RRMM. In 2015 Stewart et al. reported ORR of 87.1% vs. 66.7% in 396 patients treated with Carflizomib (K), Lenalidomide (R), and dexamethasone (d) compared to 396 patients treated with Rd alone. Lonial et al. reported ORR of 79% vs 66% for Eltozumab + Rd (n321) vs Rd (n=325). In 2016 San-Miguel et al. treated 387 patients with bortezomib, panobinostat + d, and 381 patients with bortezomib + d, with ORR of 40.3% vs. 35.8%. Shah J et al. compared Pembrolizumab, pomalidomide + d (n=125) to pomalidomide + d (n=124) with ORR of 34% vs 40% respectively. In 2018, Elotuzumab, pomalidomide (P) + d (n=60) vs. Pd (n=57) combination studied by Dimopoulos et al. resulted in an ORR of 53% vs. 26%. In 2019 Schjesvold et al. compared isatuximab, Pd (n=154), with Pd (n=153) with an ORR of 60% and 35%, respectively. Most recently, in 2020, Kumar et al. reported ORR of 82% with venetoclax, bortezomib (V) +d (n=194) compared to ORR of 68% with Vd (n=97). Mateos et al. reported ORR of 85% with VDd (n=251), vs 63% with Vd (n=247). Bahlis et al. reported ORR of 92.9% in 268, and Suzuki et al. reported ORR of 90.2% in 52 patients treated with DRd vs. ORR of 76.4% in 283 and ORR of 72.1% in 44 patients treated with Rd alone. In another trial, Dimopoulos et al. resulted in an ORR of 53% with KDd (n=312) compared to 75% with Kd (n=154). A summary of adverse effects is listed in table. Conclusions: Three drug regimen showed better results compared to two-drug regimens with a similar safety profile. A longer follow-up of these trials is needed to confirm this. Author Grade 3-4 AEs Stewart et al. Neutropenia 34%, Anemia 17%, thrombocytopenia 12%, pneumonia 14% Lonial et al. Anemia 19% Thrombocytopenia 19% neutropenia 34%, fatigue 8% San-Miguel et al. Diarrhea 25%,Peripheral neuropathy 18%, Fatigue or asthenia 24%, Thrombocytopenia 68%, Anemia 18%, leukopenia 24%. Dimopoulos et al. Anemia 10%, neutropenia (13%), Thrombocytopenia (8%), pneumonia (5%) Schjesvold et al. Infusion reaction 2%, Diarrhea 2%, Thrombocytopenia 31%, Anemia 32%, leukopenia 85%. Kumar et al. Neutropenia 18%, Anemia 15%, thrombocytopenia 15% diarhhea 15%, pneumonia 14% Mateos et al. Thrombocytopenia 46%, Anemia 16%,Neutropenia 14%, Pneumonia 10%, Hypertension 7 % A summary of Adverse effects of three drug combination therapy in RRMM.