Outcomes and associated factors after melphalan 140 mg/m² autologous hematopoietic cell transplantation for multiple myeloma in patients over 70 years of age

Abstract Background High-dose melphalan (140 mg/m²) followed by autologous hematopoietic cell transplantation (auto-HCT) is a standard consolidation strategy for multiple myeloma (MM), including in selected older adults. Limited data exist on outcomes and predictive factors in patients aged 70 years or older. This study evaluated clinical factors and outcomes following reduced-dose melphalan conditioning in this population.Methods A retrospective multicenter analysis was conducted on patients aged ≥70 years with MM who underwent auto-HCT between 2013 and 2017, using Center for International Blood and Marrow Transplant Research (CIBMTR) registry data (P-5297, Munshi et al., 2020). Baseline characteristics were summarized with descriptive statistics (medians and ranges for continuous variables, frequencies for categorical variables). Treatment-related mortality (TRM), relapse, disease-free survival (DFS), and overall survival (OS) were assessed using Cox proportional hazards models. Age was analyzed as a continuous variable, with multivariable models adjusted for Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Karnofsky performance status, International Staging System (ISS) stage, disease status at transplant, sex, and race/ethnicity. Analyses were performed using Stata 18, with significance set at p < 0.05.Results The analysis included 1,224 MM patients aged ≥70 years undergoing auto-HCT. Mean age was 73.2 years (SD ±2.3); 59.6% were male, and 82.7% were White. Most had Karnofsky performance status ≥90 (60.4%) and ISS Stage III disease (52.9%). Pre-transplant HCT-CI was ≥3 in 55.6%. Disease status at transplant was stringent/complete response (13.8%), very good partial response (41.7%), partial response (37.4%), or stable/progressive disease (6.9%). At 24 months, TRM was 4.6%, relapse occurred in 26%, DFS was 69.3%, and OS was 87.8%. In univariable analysis, higher HCT-CI was associated with increased TRM (HR 1.20, p = 0.008), lower Karnofsky score (<90) with worse OS (HR 1.58, p = 0.010) and borderline worse DFS (HR 1.24, p = 0.046), and ISS Stage III with increased relapse (HR 1.35, p = 0.011), shorter DFS (HR 1.37, p = 0.003), and worse OS (HR 1.64, p = 0.004). Age, sex, race/ethnicity, and disease status were not significant in univariable models. In multivariable analysis, age was not associated with TRM (HR, 1.03; p = 0.641), relapse (HR, 1.01; p = 0.715), DFS (HR, 1.01; p = 0.550), or OS (HR, 1.05; p = 0.156). Higher HCT-CI predicted increased TRM (HR 1.25, p = 0.003) but not relapse, DFS, or OS. Karnofsky score <90 was associated with worse OS (HR 1.46, p = 0.046) and trended toward worse DFS. ISS Stage III predicted higher relapse (HR 1.32, p = 0.023), worse DFS (HR 1.32, p = 0.012), and reduced OS (HR 1.59, p = 0.011). Sex, race/ethnicity, and disease status were not significant in multivariable models.Conclusions Melphalan 140 mg/m² followed by auto-HCT is feasible in MM patients aged ≥70 years. Age alone did not predict adverse outcomes. Higher HCT-CI, lower Karnofsky performance status, and ISS Stage III were significant determinants of worse outcomes, emphasizing the importance of comprehensive risk stratification beyond age in selecting older adults for auto-HCT.