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Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma

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Abstract

We report the first clinical investigation conducted in Japan to confirm the safety, tolerability, and pharmacokinetics of ixazomib alone and combined with lenalidomide–dexamethasone (Rd) in Japanese patients with relapsed/refractory multiple myeloma. Adult patients with measurable disease and ≥2 prior lines of therapy received oral ixazomib 4.0 mg on days 1, 8, 15 alone or combined with lenalidomide 25 mg on days 1–21 and dexamethasone 40 mg on days 1, 8, 15, 22 in 28-day cycles. Fourteen patients who had received a median of seven prior therapies were enrolled (seven per cohort). One of six evaluable patients in each cohort experienced dose-limiting toxicities [diarrhea, nausea, hypokalemia, hypertension, thrombocytopenia, hyponatremia (ixazomib cohort); thrombocytopenia, and neutropenia (ixazomib + Rd cohort)]. The most common drug-related adverse events were neutropenia, thrombocytopenia, leukopenia, and lymphopenia. Drug-related grade ≥3 adverse events occurring in ≥3 patients per cohort were (ixazomib/ixazomib + Rd cohort, n): neutropenia (4/2), thrombocytopenia (3/2), and lymphopenia (5/2). Ixazomib was rapidly absorbed with a median T max of approximately 1–2-h post-dose, and had a geometric mean terminal half-life of 5–6 days. Of 13 response-evaluable patients, one achieved a partial response (duration ∼38 weeks; ixazomib cohort) and seven had stable disease.

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Acknowledgements

This work was funded by Takeda Pharmaceutical Company Limited. The authors would like to thank all the patients who participated in this study and the staff at all investigational sites. The authors would also like to acknowledge Victoria A. Robb of FireKite, an Ashfield company, part of UDG Healthcare plc, which was funded by Takeda Pharmaceutical Company Limited, and complied with Good Publication Practice 3 ethical guidelines (Battisti WP, et al. Ann Intern Med. 2015; 163: 461–4).

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Authors and Affiliations

  1. Department of Hematology, Japanese Red Cross Medical Center, 4-1-22 Hiroo Shibuya-ku, Tokyo, 150-8935, Japan

    Kenshi Suzuki

  2. Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Gunma, Japan

    Hiroshi Handa

  3. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan

    Takaaki Chou

  4. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Kenichi Ishizawa

  5. Clinical Pharmacology Department, Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan

    Takatoshi Takubo

  6. Oncology Clinical Research Department, Oncology Therapeutic Area Unit for Japan and Asia, Takeda Pharmaceutical Company Limited, Osaka, Japan

    Yoichi Kase

Authors
  1. Kenshi Suzuki
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  2. Hiroshi Handa
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  3. Takaaki Chou
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  4. Kenichi Ishizawa
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  5. Takatoshi Takubo
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  6. Yoichi Kase
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Correspondence to Kenshi Suzuki.

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Conflict of interest

Drs. Suzuki and Handa have no conflicts to disclose. Dr. Chou received honoraria from Celgene, Bristol-Meyers-Squibb, Novartis, and Takeda. Dr. Ishizawa received personal fees for activities outside the submitted work from Kyowa Kirin, Novartis, Cyugai, Takeda, and Celgene. Drs. Takubo and Kase are both employees of Takeda Pharmaceutical Company Limited.

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Suzuki, K., Handa, H., Chou, T. et al. Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol 105, 445–452 (2017). https://doi.org/10.1007/s12185-016-2149-1

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  • DOI: https://doi.org/10.1007/s12185-016-2149-1

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