Autologous hematopoietic cell transplantation (autoHCT) remains a therapeutic option for multiple myeloma (MM) at relapse. We retrospectively analyzed 650 patients who underwent delayed (n = 335) or salvage (n = 315) autoHCT at a single center from 2006-2023. Median age was 61.4 years; 22% were Black, and 21% had high-risk cytogenetics. Forty-nine percent received >3 prior therapy lines, and 33% were lenalidomide-refractory. Non-relapse mortality was 3% at day 100 and 4% at 1 year. Median progression-free survival (mPFS) was 17.5 months and median overall survival (mOS) 47.3 months, with no significant difference between delayed and salvage autoHCT (mPFS 16.3 vs. 19.1 months; mOS 43.2 vs. 50.8 months). In salvage autoHCT, transplant ≥24 months after first autoHCT was associated with superior outcomes (mPFS 20.6 vs. 8.4 months; mOS 54.6 vs. 12.5 months; p < 0.001). Multivariable analysis identified adverse factors for PFS and OS including high-risk cytogenetics, R-ISS stage II-III, lenalidomide- or carfilzomib-refractory disease, anti-CD38 antibody non-exposure, and >3 prior therapy lines; achieving CR post-transplant and receiving maintenance predicted improved outcomes. This largest single-center cohort demonstrates delayed or salvage autoHCT is feasible and effective, particularly for patients with prolonged first remissions, and provides a benchmark for emerging therapies in relapsed/refractory MM.
© 2025. The Author(s), under exclusive licence to Springer Nature Limited.