Finding the Sweet Spot: Melphalan Dosing for Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma in Challenging Environments

Background

Autologous hematopoietic stem cell transplantation (Auto-HSCT) is a cornerstone treatment for multiple myeloma (MM). The standard conditioning regimen includes high-dose melphalan, commonly administered at 200 mg/m² (Mel-200). However, in resource-limited settings, the reduced dose of 140 mg/m² (Mel-140) is often utilized due to concerns about cost, toxicity and supportive care capabilities. This study aims to compare the efficacy and safety of Mel-140 versus Mel-200 in Auto-HSCT for MM patients in a resource-starved multicenter setting.

Methods

This retrospective multicenter study was conducted by the Plasma cell disorders working party of the Pakistan Blood and Marrow Transplant (PBMT) group. It included MM patients who underwent Auto-HSCT between January 2009 and May 2024 across six tertiary care centers with limited resources, which came to a total of 271 cases, of whom 198 patients had analyzable data. Patients were divided into two groups based on the melphalan dose received: Mel-140 (n=88) and Mel-200 (n=110). Post-transplant outcomes were documented as per the International Myeloma Working Group criteria. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included treatment-related toxicity and hematologic recovery. Statistical analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards models.

Results

The median age at the time of Auto-HSCT was 49.00 (IQR: 15) years. Males fromed the majority of the sample i.e., 144 (72.7%). Median PFS was 25.5 months (95% CI, 20-32) for the Mel-200 group and 15 months (95% CI, 13-18) for the Mel-140 group, (p=0.013). Median OS was 30 months (95% CI, 24-38) for Mel-200 and 22 months (95% CI, 17-29) for Mel-140, (p=0.083). Time to neutrophil recovery was similar across the groups, (p=0.480), while platelet recovery was significantly slower with Mel-200, (p=0.031). Frequency of engraftment failure was similar across the groups, (p<0.050). There was no difference between the groups with regards to mortality occurring secondary to infection, (p=0.802), or relapse, (p=0.324).

Conclusions

In a resource-starved multicenter setting, Mel-200 provided a statistically significant improvement in PFS compared to Mel-140 but there was no difference in OS. Mel-200 was associated with a slower platelet recovery. Death from infections and relapses were similar across both groups. These findings suggest that while Mel-200 is slightly more efficacious, Mel-140 remains a viable alternative for centers with limited supportive care resources. Further prospective studies are warranted to confirm these results and to optimize conditioning regimens for MM in resource-constrained environments, as well as look at intermediate doses to attain the best of both worlds in terms of frequency of infections and occurrence of relapses.

No relevant conflicts of interest to declare.