Impact of doublet post-transplant maintenance on outcomes in multiple myeloma: A propensity score matching analysis

Post-transplant maintenance therapy is a cornerstone of care for transplant-eligible patients with multiple myeloma (MM). While lenalidomide/bortezomib has been used as maintenance, clinical trials suggest that doublet maintenance may provide additional benefit, particularly in high-risk disease. Real-world evidence remains limited. We conducted a single-center retrospective analysis of patients with MM who underwent single autologous stem cell transplantation (ASCT) followed by maintenance therapy between 2015 and 2023. Doublet maintenance was defined as ≥2 agents and monotherapy maintenance as a single agent; dexamethasone was excluded from both definitions. The primary outcomes were event-free survival (EFS) and overall survival (OS). To mitigate treatment allocation bias, propensity score matching (PSM) was used to generate a pseudopopulation of monotherapy maintenance patients with characteristics comparable to those receiving doublet therapy. A total of 410 patients were included (doublet, n = 80; monotherapy, n = 330). The most common doublet and monotherapy regimens were bortezomib-lenalidomide (n = 46, 58%) and lenalidomide (n = 159, 48%), respectively. In the PSM analysis, doublet maintenance was associated with superior EFS (HR 0.58, p = 0.022; aHR 0.48, p = 0.007) and OS (HR 0.45, p = 0.022; aHR 0.47, p = 0.029). In this real-world analysis, doublet maintenance after ASCT was associated with superior EFS and OS, supporting broader consideration of this approach in MM.