Propylene Glycol-Free Melphalan May Induce Higher Remission Rates in Multiple Myeloma Patients Undergoing Autologous Transplantation

    Background: In a recent phase IIa open-label, randomized, cross-over design study, we evaluated the pharmacokinetics of Propylene Glycol-Free Melphalan (PG-free Mel) HCL and Alkeran in multiple myeloma patients undergoing transplantation. In this study, we have shown through statistical tests of the geometric means of AUC that PG-free Mel was bioequivalent to Alkeran, and provided marginally higher blood drug levels. Hypothesis: Because this new formulation is associated with marginally higher blood drug levels and because melphalan is associated with a linear dose-response curve, we speculated that patients treated on study would have a better multiple myeloma response compared to matched controls. Goal: To assess day +100 multiple myeloma responses from the study patients (N=24) receiving PG-free Mel conditioning in combination with Alkeran. Responses were assessed based on International Uniform Response Criteria for Multiple Myeloma. Comparison was made to a matched cohort of patients who received conventional melphalan. Methods: We compared the study patient responses to matched controls (N=24) treated exclusively with Alkeran or generic melphalan conditioning within the same time frame in a case-control study design. The controls were matched to study population based on disease stage, age, and pre-transplant response. Results: The study population and the control cohort were well matched in terms of age, gender, disease stage, and pre-transplant response. However, the study population had higher-risk cytogenetics (10 vs 3). Overall response (CR, VGPR, and PR) was higher in the study population (22 vs 19). While no patient on the study progressed within 100 days of transplant, 3 patients in the matched cohort progressed within 100 days. After a median follow up of 650 days in the study patients and 409 days in the control cohort, 23 patients on the study and 22 patients in the matched cohort were reported alive. Seven patients on the study, while 8 patients in the matched cohort progressed during follow up. Conclusion: Compared to matched controls, PG-free Mel, as part of the melphalan conditioning regimen, achieved higher remission rates and less disease progression at day 100 post autologous transplant for multiple myeloma.