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.