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High-Intensity Maintenance Post Autologous Stem Cell Transplant Is Independently Associated with Improved Event-Free Survival in Multiple Myeloma

Year: 2025

Type: article

Abstract: Following induction therapy, consolidative autologous stem cell transplant (ASCT) and post-transplant maintenance remain a cornerstone for eligible patients with multiple myeloma (MM). Historically, lenalidomide or bortezomib-based monotherapy maintenance has been the standard of care. More aggressive maintenance regimens may be associated with improved outcomes and are often recommended for patients with high-risk MM (Joseph et al 2020). We examined the impact of high intensity maintenance (HIM) therapy, utilizing propensity score matching (PSM) to determine its impact on those who received it. We conducted a single-center, retrospective study of MM patients who underwent single ASCT followed by maintenance therapy. HIM was defined as a maintenance regimen with >1 agent, excluding dexamethasone . Standard-intensity maintenance (SIM) was defined as a single agent, excluding dexamethasone . The primary outcome of interest was event-free survival (EFS), with failure events defined as death, progression, or new non-maintenance treatment. To assess outcomes, optimal full PSM was employed to create a pseudo-population of patients receiving SIM with similar characteristics as those receiving HIM. Covariates in the PSM model included CD34 infusion dose, pre-ASCT response, number of induction lines, melphalan dose, and number of high-risk cytogenetic abnormalities (HRCA), namely t(4;14), t(14;16), t(14;20), del(17p), and amp(1q). A total of 412 patients (HIM, n=79; SIM, n=333) were included. The most common HIM and SIM regimens were bortezomib/lenalidomide (n=40, 51%) and lenalidomide (n=187, 56%), respectively. HIM was primarily given due to the presence of >1 HRCA (odds ratio 8.18, p<0.001). Following PSM, the resulting baseline characteristics for HIM and SIM were similar in terms of age, number of induction lines, CD34 cell dose, percentage of R-ISS 3, number of HRCAs, percentage with circulating plasma cells, and melphalan dose. With PSM applied, the HIM cohort was associated with a significantly reduced hazard of EFS in both univariate (hazard ratio (HR) 0.58, 95% CI 0.35-0.96, p=0.033) and multivariable (adjusted HR 0.58, 95% CI 0.34-0.99, p=0.045) models (Panel A). A multivariable sensitivity analysis using the original dataset (adjusted for the PSM covariates) confirmed these results (adjusted HR 0.60, 95% CI 0.37-0.95, p=0.031). With a median follow-up of 4.7 years in the PSM analysis, EFS was longer in the high-intensity group (3.2 vs. 6.7 years, p=0.033; Panel B ), with a trend toward improved overall survival (OS) (7.1 years vs. not reached, p=0.31; Panel C ). HIM was independently associated with significantly improved EFS with a trend toward improved OS. Our findings support the application of high-intensity maintenance for patients with high-risk chromosomal features, and the need for further study of risk-adapted strategies for maintenance post-ASCT.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.157