Comparative analysis of toxicity and efficacy of melphalan at doses of 140 mg/m2 VS. 200 mg/m2 as a conditioning regimen prior to autologous stem cell transplantation.

Abstract INTRODUCTION High-dose melphalan remains the standard conditioning regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM), with 200 mg/m² (Mel200) as the conventional dose. Despite its widespread use, Mel200 is associated with substantial gastrointestinal and hematologic toxicity, which can be particularly challenging in older patients or those with significant comorbidities. Dose reduction to 140 mg/m² (Mel140) has been proposed to enhance tolerability; although its effects on efficacy and toxicity has not been fully established. MATERIALS AND METHODS A retrospective, observational, single-center study was conducted using a comparative analysis of toxicity and efficacy of melphalan as a conditioning regimen at doses of 140 mg/m² vs. 200 mg/m² in 282 MM patients who underwent ASCT between 2018 and 2024. Mel140 was used for frail patients, particularly those older (>65 years) and/or with impaired renal or cardiac function. Toxicity parameters (hematopoietic engraftment, mucositis, need for parenteral nutrition, opioid use, hospitalization) and efficacy outcomes (post-transplant response, progression-free survival [PFS], and overall survival [OS]) were assessed. Statistical analysis was performed using SPSS v26.0. RESULTS Among the 282 patients evaluated, 87 (30.9%) received melphalan 140 mg/m² (Mel140), and 195 (69.1%) received melphalan 200 mg/m² (Mel200). The median age was significantly higher in the Mel140 group (67 vs. 56 years; p<0.001). Granulocyte engraftment occurred at a median of 14.5 days (range: 10–32) in the Mel140 group and 14 days (range: 10–39) in the Mel200 group (p=0.632). Platelet engraftment was similar (14 vs. 13 days; p=0.383). There was a high incidence of febrile neutropenia, being similar in both groups (88.5% vs. 89.7%; p=0.324). Grade ≥3 mucositis occurred in 14.9% of Mel140 patients and 19.2% of Mel200 patients (p=0.44). Parenteral nutrition and opioids use was similar in both groups. Median hospital stay was also comparable (19 vs. 18 days; p=0.141). At three-month post-transplant reevaluation, complete remission (CR) rates were 60.9% (Mel140) and 67.1% (Mel200; p=0.566), with progressive disease in 2.4% and 2.2% of patients, respectively. At 12 months, CR was 64.0% (Mel140) and 71.3% (Mel200; p=0.071), increasing to 68.2% and 75.4% at 24 months (p=0.061), showing a favorable trend for Mel200 without reaching statistical significance. Cumulative relapse rates were 35.6% (Mel140) and 40.0% (Mel200; p=0.605). The median follow-up was 26 months. Overall survival (OS) was 85.1% (Mel140) and 89.7% (Mel200; p=0.429). Time to relapse was similar between groups. A total of 13 deaths (14.9%) occurred in the Mel140 group and 20 (10.3%) in the Mel200 group. No significant differences were observed in overall mortality or serious adverse events attributable to the conditioning regimen. CONCLUSIONS Although Mel140 was administered to older and more clinically frail patients, no statistically significant differences were observed in toxicity parameters, response rates, or survival outcomes. These findings suggest that Mel140 may be a valid alternative for patients with comorbidities, without substantially compromising efficacy, aligning with previous studies supporting its use tailored to clinical frailty.