Lenalidomide maintenance following autologous stem cell transplantation for treatment of multiple myeloma is a highly effective treatment strategy with large, randomized clinical trials and a meta-analysis demonstrating improved progression-free and overall survival. Our analysis of 1,256 patients from the Canadian Myeloma Research Group Multiple Myeloma Database (CMRG-DB) demonstrated a 24-month improvement in progression-free survival (58.2 months vs 34.6 months p <0.0001) and improved overall survival (NYR vs 98 months, p <0.0001). Although the survival benefits of lenalidomide maintenance are well established, many unanswered questions still exist regarding its use.
At maintenance doses, the efficacy of lenalidomide is thought to rely on its immunomodulatory effect and action against minimal residual disease (MRD) evidenced by improved rates of MRD negativity in patients on maintenance. However, the optimal duration, dosing schedule and possibility of discontinuation remain unclear. As these patients inevitably progress, the optimal sequence of subsequent therapy is of key importance. Historically, lenalidomide-exposed patients have been excluded from trials examining treatment-dose lenalidomide in the relapsed setting. This limits the generalizability of this important data to most patients as lenalidomide maintenance is increasingly adopted as the standard of care in first-line therapy. Large, retrospective datasets such as the CMRG-DB provide a critical tool to help evaluate the questions left unanswered by prospective clinical trials.
Here within we review current evidence surrounding lenalidomide maintenance and future areas of investigation.