Survival outcomes following autologous stem cell transplant with melphalan 140mg/m2 versus 200mg/m2 preparative regimens in patients with multiple myeloma

Abstract The standard preparative regimen for autologous stem cell transplant (ASCT) in multiple myeloma (MM) is 200 mg/m2 of intravenous melphalan; however, a dose of 140 mg/m2 is often used when concerns exist related to patient age, performance status, organ function, and other factors. It is unclear whether a lower dose of melphalan impacts post-transplant survival outcomes. We performed a retrospective review of 930 patients with MM who underwent ASCT with 200 mg/m2 versus 140 mg/m2 melphalan. On univariable analysis, no difference in progression-free survival (PFS) was observed, however, an overall survival (OS) benefit was observed in patients receiving 200 mg/m2 melphalan (p = 0.04). Multivariable analyses showed patients receiving 140 mg/m2 faired no worse than those receiving 200 mg/m2. While a subset of younger patients with normal renal function may achieve superior OS with a standard dose of 200 mg/m2 melphalan, these findings suggest an opportunity to individualize the ASCT preparative regimen to optimize outcomes.

[1]  H. Einsele,et al.  Long-Term Outcome of a Prospective Randomized Trial Comparing Continuous Lenalidomide/Dexamethasone with Lenalidomide/Dexamethasone Induction, MEL140 with Autologous Blood Stem Cell Transplantation and Single Agent Lenalidomide Maintenance in Patients of Age 60-75 Years with Newly Diagnosed Multiple , 2022, Blood.

[2]  S. Jagannath,et al.  Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. , 2022, The New England journal of medicine.

[3]  E. Shpall,et al.  Melphalan dose intensity for autologous stem cell transplantation in multiple myeloma , 2021, Haematologica.

[4]  Y. Efebera,et al.  Role of Stem Cell Transplantation in Multiple Myeloma , 2021, Cancers.

[5]  S. Scholl,et al.  Full Dose or Reduced Dose Melphalan (MEL) for Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): A Single Center Analysis on 187 Consecutive Patients , 2018, Blood.

[6]  P. Hari,et al.  Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival , 2018, Bone Marrow Transplantation.

[7]  W. Wiktor-Jedrzejczak,et al.  Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party , 2017, Haematologica.

[8]  Scott E. Smith,et al.  Updated analysis of CALGB 100104 (Alliance): a randomised phase III study evaluating lenalidomide vs placebo maintenance after single autologous stem cell transplant for multiple myeloma , 2017, The Lancet. Haematology.

[9]  A. Deol,et al.  BEAM Conditioning Regimen Has Higher Toxicity Compared With High-Dose Melphalan for Salvage Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. , 2015, Clinical lymphoma, myeloma & leukemia.

[10]  D. Benson,et al.  High-dose melphalan versus busulfan, cyclophosphamide, and etoposide as preparative regimens for autologous stem cell transplantation in patients with multiple myeloma. , 2007, Leukemia research.

[11]  U. Steidl,et al.  High‐dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment‐related mortality in patients with multiple myeloma: results of a randomised study , 2005, British journal of haematology.

[12]  G. Ayers,et al.  Comparison of high‐dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma , 2004, Cancer.

[13]  J. Rossi,et al.  A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma , 1996 .

[14]  Zander,et al.  High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. , 1986, Blood.

[15]  T. Mcelwain,et al.  HIGH-DOSE INTRAVENOUS MELPHALAN FOR PLASMA-CELL LEUKAEMIA AND MYELOMA , 1983, The Lancet.

[16]  D. Maloney,et al.  A randomized study of melphalan 200 mg/m2 vs 280 mg/m2 as a preparative regimen for patients with multiple myeloma undergoing auto-SCT , 2016, Bone Marrow Transplantation.

[17]  J. Abrams,et al.  A phase I dose-escalation trial of high-dose melphalan with palifermin for cytoprotection followed by autologous stem cell transplantation for patients with multiple myeloma with normal renal function. , 2013, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[18]  J. Rossi,et al.  A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. , 1996, The New England journal of medicine.