Considering Newer Agents in Managing Relapse in Resistant Myeloma
Numerous new agents and regimens for treating relapsed or refractory multiple myeloma have recently emerged. A team led by Chor Sang Chim, MBChB, MD, PhD, of the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, summarized in the journal Leukemia the results of phase III randomized controlled trials involving these novel treatments. They also offered a detailed proposed algorithm for salvage treatment in this patient population.
Based on major randomized controlled trials indicating important but, the team noted, “widely varying” progression-free survival rates, ranging from a median of 4 to 23.6 months, five approvals have been granted: the proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, and the monoclonal antibodies elotuzumab and daratumumab. Continuing under investigation for resistant myeloma in high-quality trials are anti-CD38 antibodies such as daratumumab, isatuximab, and MOR202; the oral small-molecules venetoclax and selinexor; and the anti–PD-1 checkpoint inhibitor pembrolizumab.
Taking all the approved therapies here into consideration, as well as salvage autologous stem cell transplantation and chimeric antigen receptor T-cell therapy, Dr. Chim and colleagues introduced their treatment algorithm for relapse management: “The regimens are recommended based on efficacy (by hazard ratio in the respective randomized controlled trial), prior regimen used, sensitivity to prior regimens…and data from phase III studies, or at least phase II studies. A triplet is preferred whenever possible.”
“The future of [multiple myeloma] is promising as we use combinations of novel and immune therapies earlier in the disease course,” concluded the team.