Optimizing Immunomodulatory Drug With Proteasome Inhibitor Combinations in Newly Diagnosed Multiple Myeloma.

In the modern era of multiple myeloma therapeutics, proteasome inhibitor (PI) and immunomodulatory drugs (IMiDs) have replaced chemotherapy regimens for newly diagnosed multiple myeloma patients. Treatment combinations that comprise both first- and next-generation PIs, including bortezomib, carfilzomib, and ixazomib and IMiDs, including thalidomide and lenalidomide, have been evaluated in phases II and III clinical trials and have shown significant efficacy with manageable toxicity profiles. Bortezomib or carfilzomib with lenalidomide and dexamethasone (VRD and KRD) are the most promising regimens resulting in significant survival improvement. Disease and patient characteristics should lead the individualization of treatment, with the eligibility for autologous transplant being of principal importance. The addition of a monoclonal antibody to PI with IMiD combinations is currently under clinical investigation and may lead to further treatment optimization.