Proteasome inhibition in combination with immunotherapies: State-of-the-Art in multiple myeloma

Multiple myeloma (MM) is a malignant plasma cell disorder accounting for around 1.8% of all neoplastic diseases. Nowadays, clinicians have a broad arsenal of drugs at their disposal for the treatment of MM, such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, bispecific antibodies, CAR T-cell therapies and antibody-drug conjugates. In this paper we briefly highlight essential clinical elements relating to proteasome inhibitors, such as bortezomib, carfilzomib and ixazomib. Studies suggest that the early use of immunotherapy may improve outcomes significantly. Therefore, in our review we specifically focus on the combination therapy of proteasome inhibitors with novel immunotherapies and/or transplant. A high number of patients develop PI resistance. Thus, we also review new generation PIs, such as marizomib, oprozomib (ONX0912) and delanzomib (CEP-18770) and their combinations with immunotherapies.