Long-term outcomes of busulfan plus melphalan-based versus melphalan 200 mg/m2 conditioning regimens for autologous hematopoietic stem cell transplantation in patients with multiple myeloma: a systematic review and meta-analysis

Abstract

Background High-dose melphalan (HDMEL, 200 mg/m2) is considered as the standard conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). However, whether the combination of melphalan with busulfan (BUMEL) conditioning outperforms HDMEL remains controversy. Accordingly, a systematic review and meta-analysis was carried out to compare the outcomes of HDMEL and BUMEL-based conditioning regimens in newly diagnosed MM patients having undergone auto-HSCT. Methods A systematic literature search was conducted in PubMed, Embase and Cochrane Library database until July 31, 2021, to identify all eligible studies comparing progression-free survival (PFS), overall survival (OS), optimal treatment response after auto-HSCT, duration of stem cell engraftment and incidence of toxic events between patients undergoing BUMEL-based and HDMEL conditioning regimens. Hazard ratio (HR), mean difference (MD) or odds ratio (OR) corresponding to 95% confidence interval (CI) were determined to estimate outcomes applying RevMan 5.4 software. Publication biases were assessed by performing Egger’s test and Begg’s test by Stata 15 software. Results Ten studies with a total of 2855 MM patients were covered in the current meta-analysis. The results of this study demonstrated that patients having received BUMEL-based regimen was correlated with longer PFS (HR 0.77; 95% CI 0.67~0.89, P = 0.0002) but similar OS (HR 1.08; 95% CI 0.92~1.26, P = 0.35) compared with those having received HDMEL. The differences of best treatment response after auto-HSCT and duration of neutrophil or platelet engraftment did not have statistical significance between the two groups of patients. With respect to adverse effects, the patients in BUMEL-based group were less frequently subject to gastrointestinal toxicity while the patients in HDMEL group less often experienced mucositis and infection. No significant difference was observed in hepatic toxicity between the two groups of patients. Conclusions In the present study, BUMEL-based conditioning was identified as a favorable regimen for a better PFS and equivalent OS as compared with HDMEL, which should be balanced against higher incidences of mucositis and infection. BUMEL-based conditioning is likely to act as an alternative strategy to more effectively improve auto-HSCT outcomes in MM.

Busulfan, melphalan and carfilzomib high‐dose chemotherapy and autologous haematopoietic stem cell transplantation in multiple myeloma

“…The international standard for high‐dose chemotherapy before AHSCT remains melphalan at 200 mg/m 2 (Mel200) in both the up‐front and salvage second AHSCT settings. Yet intensified regimens containing busulfan, thiotepa or bendamustine with melphalan have recently challenged the Mel200 standard 3–6 …”

Busulfan/Cyclophosphamide Compared with Melphalan as a Conditioning Regimen for Autologous Transplantation of Multiple Myeloma: A Long-Term Assessment

“…Busulfan is the most commonly used drug for hematopoietic stem cell transplantation [8]. Several studies have confirmed that the conditioning regimen containing busulfan is equivalent to HDMEL in patients with MM in ASCT [9][10][11][12]. A number of investigations have explored the role of busulfan and the cyclophosphamide (BU/CY) regimen in MM allogeneic hematopoietic stem cell transplantation (allo-HSCT) and proved to be safe and reliable [13].…”