Evolving strategies in the management of transplant-eligible patients with newly diagnosed multiple myeloma

Abstract

Multiple myeloma treatment has evolved significantly with the introduction of triplet and quadruplet regimens, notably incorporating anti-CD38 antibodies. While autologous stem cell transplantation remains a cornerstone of therapy, its role in the context of increasingly effective upfront treatments is debated. Current guidelines still recommend transplant for all eligible patients, especially those with high-risk features at diagnosis, despite concerns regarding the lack of overall survival benefits and the potential long-term toxicities associated with high-dose melphalan. Delaying transplantation until first relapse has been proposed, but this approach carries the risk of patients becoming ineligible for transplantation due to worsening health or disease progression. Consolidation therapy after transplant is not strongly endorsed in recent guidelines, and studies show mixed results regarding its efficacy. Some data suggests a progression-free survival advantage with post-ASCT consolidation; others found no significant differences in outcomes among various strategies. Nonetheless, tandem transplant may be beneficial for high-risk patients. Maintenance therapy, particularly with lenalidomide, has proven effective, offering substantial progression-free and overall survival benefits. While lenalidomide remains the standard, emerging data indicate that combinations with proteasome inhibitors or anti-CD38 antibodies could enhance outcomes, particularly in high-risk populations. As our understanding of myeloma biology deepens, tailoring treatment approaches based on risk profiles and response depth will be crucial for optimizing patient outcomes.

Keywords: Immunotherapy; Quadruplets; Risk-adapted strategy; Transplant.