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

Abstract

e20039 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\xa0al. 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\xa0al. reported ORR of 79% vs 66% for Eltozumab + Rd (n321) vs Rd (n=325). In 2016 San-Miguel et\xa0al. treated 387 patients with bortezomib, panobinostat + d, and 381 patients with bortezomib + d, with ORR of 40.3% vs. 35.8%. Shah J et\xa0al. 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\xa0al. resulted in an ORR of 53% vs. 26%. In 2019 Schjesvold et\xa0al. compared isatuximab, Pd (n=154), with Pd (n=153) with an ORR of 60% and 35%, respectively. Most recently, in 2020, Kumar et\xa0al. reported ORR of 82% with venetoclax, bortezomib (V) +d (n=194) compared to ORR of 68% with Vd (n=97). Mateos et\xa0al. reported ORR of 85% with VDd (n=251), vs 63% with Vd (n=247). Bahlis et\xa0al. reported ORR of 92.9% in 268, and Suzuki et\xa0al. 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\xa0al. 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.[Table: see text]