A Phase I/II, Open-Label, Prospective, Multicenter Study to Evaluate the Efficacy and Safety of Lower Doses of Bortezomib Plus Busulfan and Melphalan as a Conditioning Regimen in Patients with Multiple Myeloma Undergoing Autologous Peripheral Blood Stem Cell Transplantation: The KMM103 Study

The Korean Multiple Myeloma Working Party

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6 Citations (Scopus)

Abstract

A phase I/II trial was conducted to explore the safety and activity of the addition of bortezomib on days -6, -3, and +1 relative to the day of autologous stem cell transplantation (ASCT) to a conditioning regimen with busulfan and melphalan (BuMel; 3.2 mg/kg/day busulfan on days -5 to -3 and 140 mg/m2/day melphalan on day -2) in patients with multiple myeloma (MM) following bortezomib-based induction chemotherapy. In phase I, doses of bortezomib (.7, 1.0, and 1.3 mg/m2) with BuMel were administered to groups of 3 patients each. No dose-limiting toxicities were observed. The maximum tolerated dose of bortezomib was 1.3 mg/m2/day. A subsequent cohort with 41 patients was analyzed in a phase II trial to identify safety and efficacy. The phase II trial showed a 75% response rate, including very good partial response (VGPR) or better, and a 55% rate of complete response (CR) at 3 months; For post-transplantation best response, an 83% rate of VGPR or better (68% CR) was observed. With a median follow-up of 31.4 months, the median progression-free survival (PFS) was 26.8 months. The probability of 2 year-PFS was 56.5%, and median overall survival (OS) could not calculated. Specifically, high-risk cytogenetics were associated with adverse survival outcomes compared with standard-risk cytogenetics (median PFS, 12.2 months versus 35.7 months, P = .039; median OS, 26.7 months versus 73.3 months; P = .086). With a median of 11 days to neutrophil engraftment and 10 days for platelet engraftment, no graft failure or delayed engrafting were observed. The most common grade 3 or severe nonhematologic adverse events included neutropenic fever (73.2%) and stomatitis (14.6%). Except for 3 patients with transplantation-related mortality due to sepsis, other adverse events were manageable. These findings demonstrate that bortezomib is safe and has a potential role in conditioning regimens in combination with BuMel for patients with transplantation-eligible MM.

Original languageEnglish
Pages (from-to)1312-1319
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number7
DOIs
Publication statusPublished - 2019 Jul

Bibliographical note

Funding Information:
The authors are grateful to all members of the Korean Multiple Myeloma Working Party. Financial disclosure: The authors have nothing to disclose. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: S.S.P. analyzed the clinical data and wrote the manuscript. J.S.K. and C.K.M. designed the study. K.K. S.J.K. J.H.L. S.S.Y. Y.C.M. J.J.L. H.S.E. and members of the Korean Multiple Myeloma Working Party contributed to the study design and analyzed the clinical data. J.S.K. and C.K.M. were involved in critically revising the manuscript for intellectual content and approved the final manuscript for submission. Financial disclosure: See Acknowledgments on page 1319.

Publisher Copyright:
© 2019 American Society for Blood and Marrow Transplantation

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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