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Phase 1 study of bortezomib in combination with melphalan and dexamethasone in Japanese patients with relapsed AL amyloidosis

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Abstract

We performed a phase 1 study to evaluate the safety and feasibility of bortezomib (BOR) with melphalan and dexamethasone (BMD) in patients with light chain amyloidosis (AL) without severe cardiac failure. Patients received BOR on a twice-weekly schedule (days 1, 4, 8, and 11 of 28-day treatment cycles) at planned doses of 1.0 (dose level 1) and 1.3 (dose level 2) mg/m2 in combination with melphalan 8 mg/m2 on days 1–4 and dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12. Dose-limiting toxicity (DLT) was evaluated at the end of cycle one, and treatment was continued for four cycles. Six patients were enrolled at dose level 1, and one showed DLT (grade 3: herpes zoster). Further 3 patients were enrolled at dose level 2, and none experienced DLT. Thus, the maximum tolerated dose was defined as BOR doses of 1.3 mg/m2 for the twice-weekly schedule. A total of 32 cycles of BMD therapy were given, and the most common hematologic toxicity was thrombocytopenia (47 %). Peripheral neuropathy was the most common non-hematologic toxicity (16 %). We demonstrated that BMD is safe and tolerable for Japanese AL patients without severe cardiac damage.

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UMIN000006604.

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Acknowledgments

This study was supported by Grants-in-Aid for Intractable Diseases from the Ministry of Health, Labour and Welfare.

Author information

Authors and Affiliations

  1. Department of Hematology, Japan Community Healthcare Organization, Kyoto Kuramaguchi Medical Center, Kyoto, Japan

    Chihiro Shimazaki & Shin-ichi Fuchida

  2. Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

    Kenshi Suzuki

  3. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Tadao Ishida

  4. Department of Nephrology and Rheumatology, Aichi Medical University School of Medicine, Nagakute, Japan

    Hirokazu Imai

  5. Department of Hematology, National Hospital Organization Nishigunma National Hospital, Shibukawa, Japan

    Morio Sawamura

  6. Department of Hematology, Kanazawa University School of Medicine, Kanazawa, Japan

    Hiroyuki Takamatsu

  7. Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School, Tokushima, Japan

    Masahiro Abe

  8. Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshihiro Miyamoto

  9. Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan

    Hiroyuki Hata

  10. Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

    Masahito Yamada

  11. Department of Neurology, Kumamoto University School of Medicine, Kumamoto, Japan

    Yukio Ando

Authors
  1. Chihiro Shimazaki
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  2. Shin-ichi Fuchida
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  3. Kenshi Suzuki
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  4. Tadao Ishida
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  5. Hirokazu Imai
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  6. Morio Sawamura
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  7. Hiroyuki Takamatsu
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  8. Masahiro Abe
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  9. Toshihiro Miyamoto
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  10. Hiroyuki Hata
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  11. Masahito Yamada
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  12. Yukio Ando
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Corresponding author

Correspondence to Chihiro Shimazaki.

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Conflict of interest

The authors would like to thank Janssen Pharmaceutical KK, Japan, for providing bortezomib for this study. The authors have no conflict of interest to declare.

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Shimazaki, C., Fuchida, Si., Suzuki, K. et al. Phase 1 study of bortezomib in combination with melphalan and dexamethasone in Japanese patients with relapsed AL amyloidosis. Int J Hematol 103, 79–85 (2016). https://doi.org/10.1007/s12185-015-1901-2

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  • DOI: https://doi.org/10.1007/s12185-015-1901-2

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