Conditioning with Busulfan + Melphalan Versus Single-Agent Melphalan for Patients with Multiple Myeloma Receiving Autologous Stem Cell Transplantation: A Propensity Score-Matched Analysis
Authors: Patel Romil , Milton Denái R. , Tanner Mark R. , Bashir Qaiser , Srour Samer A. , Saini Neeraj Y. , Lin Paul , Ramdial Jeremy , Nieto Yago , Lee Hans C. , Patel Krina K. , Gaballa Mahmoud R. , Tang Guilin , Aljawai Yosra M. , Kebriaei Partow , Thomas Sheeba K. , Orlowski Robert Z. , Champlin Richard E. , Shpall Elizabeth J. , Qazilbash Muzaffar H. , Pasvolsky Oren 
Published: December 2024

Background: For patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT), high dose melphalan has been the standard conditioning for many years. A prospective randomized clinical trial at our institution compared the outcomes of patients who received busulfan + melphalan (BuMel) to melphalan 200mg/m2 (Mel200) showed longer progression-free survival (PFS) in the BuMel group [Bashir et al. Lancet Haematol. 2019]. In the present study we compared outcomes of patients with MM who received these two conditioning regimens as standard of care, off protocol.
Methods: We conducted a single-center, retrospective analysis of patients who underwent upfront autoHCT for MM and received either BuMel or Mel200 conditioning between 2005 to 2021. We conducted 2:1 propensity score matching (PSM) between Mel200 and BuMel patients, according to the following variables: age at autoHCT, year of autoHCT, cytogenetic risk (standard vs. high), R-ISS stage, HCT-CI (≤ 3 vs. &gt; 3), type of induction treatment, hematological response prior to autoHCT and the use of post-transplant maintenance treatment. High-risk cytogenetics were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. Clinical response, relapse, and progression were defined by the International Myeloma Working Group criteria. Primary endpoints were PFS and overall survival (OS).
Results: After matching, 262 patients in the BuMel group were compared to 524 in the Mel200 group. Patients in the two groups were well-matched for their baseline characteristics. One hundred and sixty (61%) patients in the BuMel group and 285 (54%) in the Mel200 group were male (p=0.08) and the median age at autoHCT was 59.1 and 59.4 years (p=0.53), respectively. There was no significant difference between the two conditioning groups in rates of high-risk cytogenetics (54% vs. 50%; p=0.26), revised international staging system (R-ISS) III (11% vs. 9%; p=0.42), type of induction regimen (VRD: 37% vs. 34%, KRD: 25% vs. 21%; p=0.30) or hematological response prior to autoHCT (CR: 18% vs. 16%, VGPR 45% vs. 45%; p=0.87).
There was no significant difference in CR or ≥VGPR between the BuMel and Mel200 groups at day 100 [(odds ratio (OR) 1.07, 95% confidence interval (CI) 0.79-1.45; p=0.68) and (OR 0.96, 95% CI 0.67-1.40; p=0.85), respectively] or at best post-transplant response [(OR 1.00, 95% CI 0.75-1.35; p=0.98) and (OR 1.09, 95% CI 0.66-1.79; p=0.74), respectively].
Moreover, there was no significant difference in PFS (hazard ratio (HR) 0.96, 95% CI 0.73-1.24;p=0.74) or OS (HR 1.03, 95% CI 0.72-1.46;p=0.88) between the two conditioning groups.
Within the subgroup of patients with high-risk cytogenetics, we did not observe any difference in PFS (HR 0.77, 95% CI 0.57-1.05; p=0.10) or OS (HR 0.98, 95% CI 0.63-1.52; p=0.94) between the BuMel and Mel200 groups. Similarly, within the subgroup of patients with R-ISS III, there was no significant difference in PFS (HR 1.11, 95% CI 0.57-2.17; p=0.76) or OS (HR 1.37, 95% CI 0.58-3.21; p=0.47) between the two conditioning groups.
Conclusions: In this real-world PSM analysis of patients with MM who received upfront autoHCT, we did not observe a significant difference in response rates or survival outcomes between patients who received conditioning with either BuMel or Mel200, including in subsets of patients with high-risk cytogenetics and R-ISS stage III.