Management of multiple myeloma in the relapsed/refractory patient

Abstract

The introduction of proteasome inhibitors (PIs), such as bortezomib (BTZ), and immunomodulatory drugs (IMiDs), including thalidomide (THAL) and lenalidomide (LEN), as first-line therapies in multiple myeloma (MM) has markedly improved the clinical outcomes of patients. However, MM remains incurable, and most patients eventually relapse. Moreover, prognosis is poor in patients who exhibit resistance to BTZ or LEN, and novel therapeutic approaches for such patients are urgently needed. Currently, the following six drugs are available for use in relapsed patients: second generation PIs (carfilzomib and ixazomib), an IMiD (pomalidomide), a histone deacetylase (HDAC) inhibitor (panobinostat), and two monoclonal antibodies (elotuzumab and daratumumab). The choice of treatment should be individualized based on certain factors, such as age, presence of comorbidities, frailty, cytogenetic risk, efficacy and toxicity of prior treatments, and the duration of the previous response. A course of triplet therapy containing two novel agents along with DEX is recommended, on first relapse, in fit and healthy patients, whereas doublet therapy is preferred for unfit or frail patients. Retreatment of relapsed/refractory MM (RRMM) with monoclonal antibodies and IMiDs is promising because these drugs have immunostimulatory effects. In addition, novel agents, including an anti-BCMA antibody-drug conjugate, are being studied. Clinical trials are needed to define the optimal treatment strategy for RRMM.