Abstract
This phase I open-label study evaluated the tolerability of pegylated liposomal doxorubicin (PLD) and bortezomib combination in Japanese patients with relapsed or refractory multiple myeloma. Eligible patients (≥20 years) who had ≥1 line of prior chemotherapy received bortezomib 1.3 mg/m2 rapid intravenous infusion on days 1, 4, 8 and 11 (each 21-day cycle), followed by PLD 30 mg/m2 intravenous infusion on day 4 (each cycle), up to 6 cycles. Dose-limiting toxicity (DLT), defined as Grade 4 hematologic or Grade ≥3 non-hematologic, was evaluated through end of day 21. All three patients enrolled in the study developed DLTs [Grade 4 thrombocytopenia (n = 2) and Grade 3 ileus (n = 1)]. The study was, therefore, terminated without adding new patients, as per protocol-specified criteria. The most common Grade 3–4 adverse events (AEs) were hematologic, including thrombocytopenia, leucopenia, and neutropenia. The treatment was prematurely discontinued in all three patients due to AEs: Grade 3 bronchiolitis (serious AE), Grade 3 peripheral sensory neuropathy, and Grade 2 stomatitis. All patients achieved partial response (efficacy, secondary endpoint). In conclusion, the tolerability of PLD and bortezomib combination at dose levels approved in various countries was not confirmed in relapsed or refractory multiple myeloma patients from Japan.
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Acknowledgments
We acknowledge Ramji Narayanan (SIRO Clinpharm Pvt. Ltd.) for writing assistance and Namit Ghildyal, PhD (Janssen Research and Development, LLC) for additional editorial support for the development of this manuscript. The authors also thank the study participants, without whom the study would never have been accomplished. The study was funded by Janssen Research and Development Division, Janssen Pharmaceutical KK, Japan.
Conflict of interest
Drs. Iida and Kusumoto received research funding for this study from Janssen Pharmaceutical KK, Japan through their institutions. Dr. Iida received personal fees from Janssen Pharmaceutical Company; grants and personal fees from Celgene K.K., Ono Pharmaceutical Co., Ltd.; grants from Kyowa Hakko Kirin Co. Ltd., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., and Taiho Pharmaceutical Co., Ltd., outside the submitted work. Dr. Sunami received grants and personal fees from Celgene K.K.; grants from Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., outside the submitted work. Dr. Inagaki is an employee of Janssen Pharmaceutical KK, Japan.
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Clinical trial registration: NCT01371227.
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Kusumoto, S., Sunami, K., Inagaki, M. et al. Phase I study of pegylated liposomal doxorubicin in combination with bortezomib for Japanese patients with relapsed or refractory multiple myeloma. Int J Hematol 101, 578–584 (2015). https://doi.org/10.1007/s12185-015-1773-5
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DOI: https://doi.org/10.1007/s12185-015-1773-5