The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

Simple Summary Multiple myeloma remains an essentially incurable blood cancer. New patients with multiple myeloma are often treated with induction chemotherapy, stem cell transplantation, and then maintenance chemotherapy. As the immune system of the patient is a critical element in controlling the growth of tumor cells, this review aims to summarize what is known regarding the effects on the immune system of the commonly employed drugs used in the induction chemotherapy phase of the treatment-melphalan, dexamethasone, lenalidomide, and bortezomib. Understanding the effects of each drug on the immune system could lead to devising rational combinations of these drugs, which may lead to longer survival of patients with this cancer. Current standard frontline therapy for newly diagnosed patients with multiple myeloma (NDMM) involves induction therapy, autologous stem cell transplantation (ASCT), and maintenance therapy. Major efforts are underway to understand the biological and the clinical impacts of each stage of the treatment protocols on overall survival statistics. The most routinely used drugs in the pre-ASCT "induction" regime have different mechanisms of action and are employed either as monotherapies or in various combinations. Aside from their direct effects on cancer cell mortality, these drugs are also known to have varying effects on immune cell functionality. The question remains as to how induction therapy impacts post-ASCT immune reconstitution and anti-tumor immune responses. This review provides an update on the known immune effects of melphalan, dexamethasone, lenalidomide, and bortezomib commonly used in the induction phase of MM therapy. By analyzing the actions of each individual drug on the immune system, we suggest it might be possible to leverage their effects to rationally devise more effective induction regimes. Given the genetic heterogeneity between myeloma patients, it may also be possible to identify subgroups of patients for whom particular induction drug combinations would be more appropriate.