Introduction:

Multiple myeloma (MM) is a hematological malignancy characterized by the abnormal proliferation of monoclonal plasma cells in the bone marrow, leading to symptoms such as bone pain, hypercalcemia, and renal dysfunction. A significant advancement in the treatment of MM is autologous hematopoietic stem cell transplantation, which has been effectively utilized to improve patient outcomes. This meta-analysis aims to explore the comparative efficacy and safety profile of Busulfan plus low dose Melphalan (BUMEL) versus High dose Melphalan (HDMEL) as a conditioning regimen for Autologous Hematopoietic stem cells transplantation in patients of Multiple Myeloma.

Methods:

A comprehensive literature review including 13 final studies was conducted using PubMed, Cochrane, and Embase. We included randomized controlled trials focused on patients with multiple myeloma treated with Busulfan plus low-dose Melphalan and high-dose Melphalan. A hazard ratio (HR) corresponding to a 95% confidence Interval (CI) was adopted to assess OS and PFS. The DerSimonian and Laird random effects model was used to pool Hazard ratios (HR) and dichotomous outcomes were pooled using risk ratio while continuously using Mean difference. The random effects model was used using the inverse variance method. a p-value of <0.5 was considered statistically significant.

Results:

The BUMEL-based conditioning regimen was found to be more favorable regarding progression-free survival (PFS) compared to the HDMEL regimen (HR 0.89; 95% CI 0.77-0.97, P = 0.006). However, overall survival (OS) was comparable between the two therapeutic groups, with no statistically significant difference observed (HR 1.12; 95% CI 0.82-1.43, P = 0.76). Regarding the safety profile, gastrointestinal side effects were less common with the BUMEL regimen (OR 0.81; 95% CI 0.57-0.90, P < 0.004) compared to HDMEL. Conversely, other side effects such as mucositis, infections, and hepatic toxicity were more prevalent with BUMEL-based therapy.

Conclusion:

In our meta-analysis, the BUMEL-based regimen demonstrated higher effectiveness in terms of progression-free survival (PFS), with this comparison being statistically significant. Although overall survival (OS) also favored the BUMEL-based therapy, there was no statistically significant difference between the two groups. The overall toxicity profile was higher in the BUMEL group, except gastrointestinal toxicity, which was less common, thus balancing the efficacy and safety profiles between the BUMEL and HDMEL regimens.

Keywords: Autologous Hematopoietic stem cell transplantation, BUMEL, HDMEL, Multiple Myeloma.

Disclosures

No relevant conflicts of interest to declare.

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2024
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