Maintenance therapy after ASCT in newly diagnosed multiple myeloma patients: single agent versus combination drugs

Introduction: Maintenance therapy plays a crucial role in prolonging progression-free survival and overall survival in multiple myeloma. Lenalidomide remains the gold standard, as demonstrated in phase 3 trials, consistently showing superior survival compared to observation or placebo. However, both established and novel agents–such as thalidomide and pomalidomide, proteasome inhibitors (PIs), monoclonal antibodies (moAbs), and bispecific antibodies–have been investigated as alternatives to assess their efficacy and safety. Areas covered: This review delivers a comprehensive analysis of the current landscape of maintenance strategies in MM and presents the available evidence supporting the efficacy of novel agents, both as monotherapy and in combination. Expert opinion: Maintenance therapy is a critical component of MM management, capable of improving disease control and survival. Lenalidomide has demonstrated its ability to extend patients’ survival, but cumulative toxicity remains a significant concern. For high-risk patients, maintenance therapy with PIs and CD38-targeting moAbs has proven to improve outcomes. However, challenges such as quality of life, cost, accessibility, and treatment resistance persist. A minimal residual disease (MRD)-adapted maintenance strategy is desirable, particularly to enable personalized treatment approaches in clinical practice.