P-144: Busulfan plus melphalan versus high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma with high-risk features (KMM 2015)

Introduction: Despite the development of effective agents for multiple myeloma (MM), managing patients with high-risk MM (HRMM) remains challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is considered the frontline treatment for transplant-eligible patients with HRMM. This study aimed to compare the efficacy of two conditioning regimens, high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL), for upfront ASCT in newly diagnosed patients with MM and high-risk features.

Methods: This study retrospectively collected the data of patients diagnosed with MM between May 2005 and June 2021 who received ASCT with BUMEL or HDMEL conditioning from 12 institutions that participated in the KMM 2015 trial.

Results: A total of 221 patients underwent ASCT between May 2005 and June 2021, and among them, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS: not reached vs. 53.2 months; P = 0.091; median PFS: not reached vs. 31.7 months; P = 0.062). Furthermore, multivariate analysis revealed that BUMEL was significantly associated with improved PFS (hazard ratio = 0.37, 95% confidence interval = 0.15–0.89, P = 0.026). Additionally, we compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than a very good partial response (VGPR) to frontline therapy, the BUMEL group had a significantly longer median PFS compared to the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011).

Conclusions: These findings suggest that BUMEL is an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics, and it may be more suitable than HDMEL for patients with less than a VGPR to frontline therapy