Abstract
Proteasome inhibitors (PIs) in combination with immunomodulatory drugs (IMiDs) have been shown to be effective against relapsed/refractory multiple myeloma (RRMM). To determine the optimal dosing schedule of once weekly bortezomib (BTZ) combined with lenalidomide (LEN) and dexamethasone (DEX), especially in the outpatient setting, we conducted a phase I dose escalation study. A 21-day cycle of BTZ 1.3 mg/m2 on days 1 and 8, LEN 10 mg/day (cohort 1) or 15 mg/day (cohort 2) on days 1–14, and DEX 20 mg/day on days 1, 2, 8, and 9 was administered. Three patients were enrolled in each cohort. No dose-limiting toxicity was observed in either cohort. Although hematological toxicities estimated as >grade 3 were common, non-hematological toxicities of grade 3 or higher were rare. Two cases of newly diagnosed peripheral neuropathy (PN) were observed, while no grade 3/4 PN was observed. Two patients achieved partial response and two achieved stable disease. The recommended doses of BTZ and LEN were determined to be 1.3 mg/m2 and 15 mg, respectively. Combination therapy of once weekly BTZ with LEN and DEX was well tolerated and shows promise as a regimen for patients with RRMM previously treated with both PIs and IMiDs.
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Acknowledgments
We would like to thank the members of the Data Safety Monitoring Board; Dr Tetsuya Oguri (Nagoya City University Hospital) and Dr Tatsuya Yoshida (Aichi Cancer Center Hospital) for their contribution. This work was partly supported by a Grant-in-Aids for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (23791085 & 24591406), National Cancer Center Research and Development Fund (26-A-4), and the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development, AMED.
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MR. received research funding from Celgene Co., Ltd. S.I. received research funding and declares honoraria from Janssen Pharmaceutical K.K. and Celgene Co., Ltd. S.I. also received research funding from Kyowa Hakko Kirin Co., Ltd, Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical CO., Ltd, and Eli Lilly Japan K.K. T.I. received research funding from Kyowa Hakko Kirin Co., Ltd., Bayer Pharma AG, and Celgene K.K. T.I. also received honoraria from Kyowa Hakko Kirin Co., Ltd.
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Totani, H., Ri, M., Kato, C. et al. Phase I study of once weekly treatment with bortezomib in combination with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma. Int J Hematol 103, 316–321 (2016). https://doi.org/10.1007/s12185-015-1925-7
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DOI: https://doi.org/10.1007/s12185-015-1925-7