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Report of phase I and II trials of melphalan, prednisolone, and thalidomide triplet combination therapy versus melphalan and prednisolone doublet combination therapy in Japanese patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation

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Abstract

We conducted a phase I study to determine the recommended dose of thalidomide combined with melphalan plus prednisolone (MPT) and a phase II study evaluating the efficacy and safety of this MPT regimen in transplant-ineligible Japanese patients with untreated multiple myeloma. The recommended dose was determined to be 100 mg/day in the phase I study. In the phase II, randomized, double-blind, parallel-group study, patients were allocated to either MPT (n = 52) or MP (n = 51), with 21 and 29 patients completing the study, respectively. Overall response rate, the primary endpoint, was significantly higher in the MPT [40.4% (21/52 patients), 95% confidence interval (CI) 27.0–54.9%] than in the MP [19.6% (10/51 patients), 95% CI 9.8–33.1%] group (P = 0.022). Time to response was also significantly shorter in the MPT group. Incidences of hematological toxicities were similar in the two groups, suggesting that addition of thalidomide did not increase hematological toxicity. Although incidences of some non-hematological toxicities tended to be higher in the MPT group, the low incidence of ≥ Grade 3 toxicities suggests that MPT therapy was well tolerated. These results support the safety and efficacy of MPT therapy in untreated Japanese multiple myeloma patients.

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Acknowledgements

We thank all of the study participants and other relevant parties for their cooperation in conducting the present studies. We also thank to the following investigators who made important contributions to these studies: Kensuke Usuki (NTT Medical Center Tokyo), Norifumi Tsukamoto (Gunma University Hospital), Naoki Takezako (National Hospital Organization Disaster Medical Center), Hitoshi Ohno (Tenri Hospital), Morio Matsumoto (National Hospital Organization Shibukawa Medical Center), Kyoya Kumagai (Chiba Cancer Center), Akiyoshi Miwa (Tokyo-Kita Medical Center), Chisato Mizutani (Osaka Red Cross Hospital), Yutaka Okuno (Kumamoto University Hospital), Hiroshi Ikeda (Sapporo Medical University Hospital), Takuya Komeno (National Hospital Organization Mito Medical Center), Masahiro Kizaki (Saitama Medical University), Shinichiro Okamoto (Keio University Hospital), Tadao Ishida (Japanese Red Cross Medical Center), Nobuaki Dobashi (The Jikei University Daisan Hospital), Kiyoshi Ando (Tokai University Hospital), Keita Kirito (University of Yamanashi Hospital), Michihiro Uchiyama (Suwa Red Cross Hospital), Chihiro Shimazaki (Japan Community Health care Organization Kyoto Kuramaguchi Medical Center), Kensuke Ohta (Osaka Saiseikai Nakatsu Hospital), Yasunori Ueda (Kurashiki Central Hospital), Hideki Asaoku (Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital), Masaaki Noguchi (Juntendo University Urayasu Hospital), Ichiro Hanamura (Aichi Medical University Hospital), Shinsuke Iida (Nagoya City University Hospital), Masafumi Taniwaki (University Hospital Kyoto Prefectural University of Medicine), Hirohiko Shibayama (Osaka University Hospital), Masahiro Abe (Tokushima University Hospital), Japan.

Funding

This study was funded by Fujimoto Pharmaceutical Corp.

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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 Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, Japan

    Noriko Doki

  3. Department of Hematology, National Hospital Organization Sendai Medical Center, 2-8-8, Miyagino, Miyagino-ku, Sendai, Miyagi, Japan

    Kuniaki Meguro

  4. Department of Hematology, National Hospital Organization Okayama Medical Center, 1711-1 Tamasu, Kita-ku, Okayama, Okayama, Japan

    Kazutaka Sunami

  5. Department of Hematology, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki, Gifu, Japan

    Hiroshi Kosugi

  6. Department of Hematology, Miyagi Cancer Center, 47-1, Nodayama, Medeshima-shiote, Natori, Miyagi, Japan

    Osamu Sasaki

  7. Department of Hematology, Oami Municipal Hospital, 884-1 Tomita, Oami-shirasato, Chiba, Japan

    Toshiyuki Takagi

  8. Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22, Showa-machi, Maebashi, Gunma, Japan

    Hirokazu Murakami

  9. Department of Hematology/Oncology, National Hospital Organization Higashi Nagoya National Hospital, 5-101, Umemorizaka, Meito-ku, Nagoya, Aichi, Japan

    Kazuyuki Shimizu

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  1. Kenshi Suzuki
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Corresponding author

Correspondence to Kenshi Suzuki.

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Conflict of interest

K Suzuki served on scientific advisory boards and speakers’ bureaus for Takeda Pharmaceutical Co. Ltd., Bristol-Myers Squibb K. K., and received honoraria from Janssen Pharmaceutical K. K., Novartis Pharma K. K., Celgene K. K., Fujimoto Pharmaceutical Corp., and Takeda Pharmaceutical Co. Ltd. K. Sunami received research grants from Fujimoto Pharmaceutical Corp., Novartis Pharma K. K., GlaxoSmithKline K. K. Janssen Pharmaceutical K. K., Abbvie GK., Takeda Pharmaceutical Co. Ltd., Sanofi K. K., Bristol-Myers Squibb K. K., Ono Pharmaceutical Co. Ltd., MSD K. K., Alexion Pharma, Daiichi-Sankyo Co. Ltd., Celgene K. K., and honoraria from Takeda Pharmaceutical Co. Ltd., Bristol-Myers Squibb K. K., Ono Pharmaceutical Co. Ltd., Celgene K. K.Y. T. Takagi received consulting fees from Fujimoto Pharmaceutical Corp. H. Murakami received a research grant from Fujimoto Pharmaceutical Corp. and Celgene K. K., and served on scientific advisory boards and speakers’ bureaus for Celgene K. K., Sanofi K. K. and Ono Pharmaceutical Co. Ltd. K. Shimizu received consulting fees from Daiichi-Sankyo Co. Ltd. and Fujimoto Pharmaceutical Corp. N. Doki, K. Meguro, H. Kosugi and O. Sasaki declare no conflict of interest.

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Suzuki, K., Doki, N., Meguro, K. et al. Report of phase I and II trials of melphalan, prednisolone, and thalidomide triplet combination therapy versus melphalan and prednisolone doublet combination therapy in Japanese patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation. Int J Hematol 110, 447–457 (2019). https://doi.org/10.1007/s12185-019-02700-3

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  • DOI: https://doi.org/10.1007/s12185-019-02700-3

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