Approaches To Managing Relapsed Myeloma: Switching Drug Class or Retreatment With Same Drug Class?

Multiple myeloma (MM) is the second most common haematological malignancy characterised by clonal proliferation of plasma cells within the bone marrow. Despite advances in treatment options, myeloma remains incurable. Relapsed MM poses significant challenges due to clonal evolution, drug resistance, patient comorbidities and therefore complexities of therapeutic decision-making. A critical question in managing relapsed MM is whether to switch drug classes or retreat with agents within the same class. The question is present with the recent addition of three new drug classes (XPO1 inhibitors, BCMA targeted agents, GPRC5d targeted agents) to clinical practice. Switching drug classes offers the potential to target alternative disease pathways and introduce new mechanisms of action, which can be particularly beneficial in cases of limited response to previous therapies. On the other hand, retreatment within the same drug class remains an effective strategy for some patients, particularly those who previously achieved durable responses and known tolerability profile. Both approaches require careful consideration on a background of patient-specific factors such as age, comorbidities, disease burden, and quality of life. We discuss the clinical vignette of a 71-year-old male with biochemical relapse after lenalidomide maintenance; this review explores the nuanced decision-making process involved in selecting the most appropriate treatment. By taking a personalised approach and integrating the evolving therapeutic landscape with real-world considerations, this review highlights strategies to optimise outcomes while maintaining tolerability and quality of life in patients with relapsed MM.