Melphalan Plus Bendamustine Versus Melphalan Alone for Single Asct in Multiple Myeloma: a Retrospective Efficacy and Toxicity Analysis
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction In patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT), bendamustine was added to melphalan as a conditioning-intensification strategy. The effects of this approach on toxicity and post-transplant outcomes remain uncertain. Objectives The study objective was to compare toxicity, PFS, and OS between melphalan alone and melphalan plus bendamustine across cytogenetic-risk and soft-tissue subgroups. Materials and methods This retrospective study included 184 patients (melphalan, n = 77; melphalan plus bendamustine, n = 107). Toxicity, progression-free survival (PFS), and overall survival (OS) were evaluated. PFS included progression, relapse, or death; OS included death. Kaplan–Meier, log-rank, and Cox regression adjusted for age, high-risk cytogenetics, soft-tissue involvement, prior lines, and transplantation year were used. Results The intensified group included more patients with high-risk cytogenetics (29.0% vs 6.5%; p < 0.001), soft-tissue involvement (36.4% vs 20.8%; p = 0.023), and more prior lines (median 2 vs 1; p = 0.0045). Median transplantation year was 2024 versus 2019 (p < 0.001). Grade 3–4 mucositis was less frequent after intensification (29.0% vs 62.3%; p < 0.001), while infectious complications and third-line/reserve antibiotic use were not increased. Crude progression/relapse was lower (18.7% vs 46.8%; p < 0.001), although follow-up was 12.6 versus 63.6 months. Median PFS was 34.6 versus 41.3 months (p = 0.925); median OS was not reached in either group (p = 0.543). After adjustment, intensification was associated with numerical reductions of 44% in progression/death (HR 0.56, 95% CI 0.29–1.09; p = 0.087) and 51% in death (HR 0.49, 95% CI 0.21–1.15; p = 0.101). In high-risk patients (melphalan n = 5; intensified n = 31), median PFS was 18.6 versus 20.3 months (HR 0.62; p = 0.370), and OS was 28.7 months versus not reached (HR 0.55; p = 0.325), numerically favoring intensification. In standard-risk patients (n = 23 vs 39), PFS and OS medians were not reached (p = 0.724 and p = 0.707). With unknown risk (n = 49 vs 37), PFS was 32.7 versus 32.3 months (p = 0.874), and OS was 83.4 months versus not reached (p = 0.502). With soft-tissue involvement (melphalan n = 16; intensified n = 39), PFS was 9.2 versus 23.3 months (HR 0.66; p = 0.317), and OS was 34.4 versus 23.3 months (p = 0.485). Without soft-tissue involvement (n = 61 vs 68), PFS was 51.5 versus 34.6 months (p = 0.882), and OS was not reached (p = 0.543). Interaction tests were non-significant for cytogenetic risk (p = 0.724) and soft-tissue involvement (p = 0.274). Discussion Multivariable analysis showed numerical reductions in progression and death after bendamustine was added to melphalan. Favorable trends were observed in high-risk disease and for PFS with soft-tissue involvement. Non-significance may reflect limited power, including only five high-risk patients receiving melphalan alone, low event numbers, unequal follow-up, and treatment-era imbalance. These findings suggest potential benefits without increased infectious toxicity. Conclusion Bendamustine-intensified melphalan conditioning demonstrated an acceptable toxicity profile and non-significant trends towards improved adjusted PFS and OS. Potential advantages in high-risk cytogenetics and soft-tissue disease require confirmation in larger, balanced cohorts with longer follow-up.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223088621