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A phase I/II study of escalating doses of thalidomide in conjunction with bortezomib and high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma

Bone Marrow Transplantation volume 54, pages 1881–1891 (2019)Cite this article

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Abstract

A regimen of escalating doses of thalidomide, in combination with bortezomib and high-dose melphalan (mel/vel/thal), was evaluated as a conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with a prior transplant who had relapsed or achieved less than a complete remission following a prior ASCT. Thalidomide was dose escalated starting from 600 mg to 1000 mg on days −5 to −1 in a 3 × 3 design, bortezomib was administered at 1.6 mg/m2 intravenously on days −4 and −1 and melphalan 200 mg/m2 was administered on day −2. No dose-limiting toxicity was seen in the phase I portion of the trial. An additional 20 patients were enrolled at the maximum tolerated dose of thalidomide of 1000 mg daily. The overall response rate was 69% with 38% complete remission. Median PFS and OS were 9.3 and 65.4 months, respectively, with a median follow-up of 17.8 months. The most common grade 3–4 adverse events (AEs) were neutropenic fever (58.6%), mucositis (6.9%), and diarrhea (6.9%). Serious AEs included somnolence (13.8%) and tumor lysis syndrome (3.4%). The addition of high-dose thalidomide to bortezomib and melphalan as conditioning for salvage ASCT was well tolerated and was an effective conditioning regimen.

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Authors and Affiliations

  1. John Theurer Cancer Center at Hackensack Meridian, Seton Hall University School of Medicine, Hackensack, NJ, USA

    Noa Biran, Scott D. Rowley, David H. Vesole, Michele L. Donato, Andrew Pecora & David S. Siegel

  2. University of Minnesota School of Medicine, Minneapolis, MN, USA

    Shijia Zhang

  3. Novant Health, Charlotte, NC, USA

    Alan P. Skarbnik

  4. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Joshua Richter

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Correspondence to Noa Biran.

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NB—Speaker’s bureau for Celgene, Takeda, Amgen, and Janssen; Advisory Board for Takeda, Celgene, and Amgen; Research funding from Merck and Bristol Meyers Squibb; DHV—Speaker’s bureau for Takeda, Amgen, Celgene, and Janssen; JR—Speaker’s bureau for Celgene, Takeda, Janssen, Amgen, Sanofi, and BMS; DSS—Speaker’s bureau for Celgene, Takeda, and Amgen; Advisory Board and Consulting for Takeda, Celgene, Amgen, and Janssen. The other authors declare that they have no conflict of interests.

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Biran, N., Rowley, S.D., Vesole, D.H. et al. A phase I/II study of escalating doses of thalidomide in conjunction with bortezomib and high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma. Bone Marrow Transplant 54, 1881–1891 (2019). https://doi.org/10.1038/s41409-019-0534-0

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