Emerging and current treatment combinations for transplant-ineligible multiple myeloma patients

Introduction: Availability of new classes of novel agents has led to a radical switch in treatment paradigms for newly diagnosed transplant-ineligible multiple myeloma (NDTIMM) patients, providing an opportunity to significantly enhance the depth of response and extend survival outcomes. Areas covered: Treatment regimens including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and/or monoclonal antibodies (mAbs), have achieved recent regulatory approval for NDTIMM, while novel combinations and newer agents are currently being explored. This review discusses the current landscape and possible treatment development of NDTIMM. Expert opinion: Bortezomib-lenalidomide-dexamethasone (VRd), daratumumab-bortezomib-melphalan-prednisone (DaraVMP) and daratumumab-lenalidomide-dexamethasone (DaraRd) represent new standard of care (SOC) treatments for NDTIMM patients, based on phase III trials showing their superior efficacy as compared with previous SOCs. The possibility of improving results by incorporating second generation PIs or using quadruple regimens has also been explored and different trials are still ongoing. Newer agents and innovative immunotherapies targeting B-cell maturation antigen have the potential to change the therapeutic landscape in coming years. Personalized approaches based on frailty-adapted, risk-based and minimal residual disease driven paradigms are under investigation.