The treatment landscape for relapsed multiple myeloma (RRMM) has experienced an unprecedented wave of innovation. Implementation of numerous new substances and drug classes with different modes of action is made possible in routine clinical practice. Next generation proteasome inhibitors, monoclonal antibodies, as well as first in class agents such as selinexor and venetoclax have widened the therapeutic spectrum. This has led to an increase in progression-free and overall survival. Consequently, new challenges for treating physicians in choosing the right treatment at the right stage of the disease have been generated. Several trials support the use of novel agents in the frontline treatment of newly diagnosed multiple myeloma. The use of lenalidomide or bortezomib as a backbone in the first-line setting, requires strategies for treatment once these patients relapse and are refractory to these drugs. Despite the variety of options, selecting the optimal treatment strategy is difficult, since multiple factors have to be considered: patient-specific factors such as age and co-morbidities, as well as myeloma/tumor specific factors such as cytogenetics and relapse kinetics. This review intends to summarize the existing data and guidelines regarding the optimal sequencing of treatments of RRMM using already approved agents as well as agents under investigation.
Keywords: extramedullary disease; high-risk cytogenetics; multi-refractory; multiple myeloma; relapsed and refractory.