The role of maintenance therapy and its cessation in patients with multiple myeloma

Lenalidomide maintenance therapy remains a cornerstone of post-induction treatment in multiple myeloma (MM), supported by various landmark trials demonstrating improved outcomes with lenalidomide maintenance over observation or placebo following autologous stem cell transplant (ASCT). Despite advancements in the MM treatment landscape, including the integration of quadruplet induction therapies and measurable residual disease (MRD) assessment to define deep responses, most maintenance strategies continue to focus on maintenance intensification rather than de-escalation. With an increasing number of patients achieving sustained deep responses, the optimal application and duration of maintenance therapy deserve reevaluation. This manuscript explores the rationale behind maintenance therapy in MM, examining the long-term benefits and adverse effects of ongoing treatment, state-of-the-art approaches to maintenance, and MRD-driven approaches to potentially de-escalate, discontinue, or eschew maintenance altogether.