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Japanese phase II study of rituximab maintenance for untreated indolent B-cell non-Hodgkin lymphoma with high tumor burden

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An Erratum to this article was published on 28 November 2016

Abstract

Recent large-scale randomized clinical trials in Europe and the US demonstrated that maintenance therapy with rituximab significantly improved the progression-free survival (PFS) in indolent B-cell non-Hodgkin lymphoma (B-NHL) patients, especially those with follicular lymphoma (FL). However, rituximab maintenance has not been approved in Japan, because there are no clinical data supporting the benefit of rituximab maintenance in Japanese patients. Therefore, we conducted a single-arm, multicenter bridging study in previously untreated indolent B-NHL patients with high tumor burden. The primary endpoint was 4-year PFS and was expected to be 70 % based on previous studies. Sixty-two patients, including 55 FL patients, were enrolled and received induction therapy with CHOP combined with rituximab (R-CHOP). Fifty-eight patients responding to R-CHOP induction received rituximab at 375 mg/m2 every 8 weeks for 2 years as for the rituximab maintenance arm in the PRIMA study. A 4-year PFS of 69.8 % was obtained (95 % confidence interval 55.9–80.0 %). Rituximab maintenance was well tolerated and common adverse events were infections, neutropenia, and/or leukopenia that were manageable with conventional supportive care. No patients died. These data were compatible with the PRIMA data. R-CHOP induction followed by rituximab is useful in Japanese patients with untreated indolent B-NHL having high tumor burden.

Clinical trial number UMIN000001191

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Acknowledgments

This study was supported by Zenyaku Kogyo (Tokyo, Japan). The authors thank the patients and their families and all the investigators, including the physicians, nurses, clinical research coordinators (CRC), and laboratory technicians in the participating institutions of this multicenter trial. The authors are grateful to Drs K. Toyama (Tokyo Medical College, Tokyo, Japan), N. Horikoshi (Juntendo University School of Medicine, Tokyo, Japan), and M. Mori (Japanese Red Cross Medical Center, Tokyo, Japan) for their critical review of the clinical data as members of the Independent Data and Safety Monitoring Committee. The authors are also grateful to Drs S. Nakamura (Nagoya University Graduate School of Medicine, Nagoya, Japan), and Y. Matsuno (Hokkaido University Hospital, Sapporo, Japan) for their histopathological review as members of the Central Pathology Review Committee, and M. Matsusako (St. Luke’s International Hospital, Tokyo, Japan) for their central radiological review as members of the CT Review Committee. The authors also acknowledge K. Endo, H. Harada, T. Ito, I. Okugaito, M. Watanabe, M. Abe, T Oba, S. Kamiyama, and T. Kayo (Zenyaku Kogyo) for their help with data collection and statistical analysis.

The authors would like to thank Ms Reiko Yamaura and Dr J. Ludovic Croxford of Edanz Group Ltd. for providing English writing support, which was funded by Zenyaku Kogyo.

Author information

Author notes

  1. Michinori Ogura

    Present address: Department of Hematology, Tokai Central Hospital, Kakamigahara, Japan

  2. Yoshiaki Kuroda

    Present address: Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan

  3. Naokuni Uike

    Present address: Department of Palliative Care, Saga Prefectural Hospital Koseikan, Saga, Japan

  4. Akihiro Tomita

    Present address: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan

  5. Takashi Terauchi

    Present address: Department of Nuclear Medicine, Cancer Institute Hospital, Tokyo, Japan

Authors and Affiliations

  1. Division of Hematology/Oncology, Gunma Cancer Center, 617-1 Takabayashinishicho, Ohta, 373-8550, Japan

    Tadahiko Igarashi

  2. Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan

    Michinori Ogura

  3. Department of Hematology, National Cancer Center Hospital East, Chiba, Japan

    Kuniaki Itoh

  4. Department of Hematology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Masafumi Taniwaki

  5. Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan

    Kiyoshi Ando

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

    Yoshiaki Kuroda

  7. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

    Kazuhito Yamamoto

  8. Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan

    Naokuni Uike

  9. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Akihiro Tomita

  10. Department of Hematology, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan

    Hirokazu Nagai

  11. Department of Hematology, National Hospital Organization, Hokkaido Cancer Center, Sapporo, Japan

    Mitsutoshi Kurosawa

  12. The University of Tokyo, Tokyo, Japan

    Shigeo Mori

  13. Department of Radiology, International University of Health and Welfare Mita Hospital, Tokyo, Japan

    Shigeru Nawano

  14. Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan

    Takashi Terauchi

  15. Faculty of Science and Engineering, Chuo University, Tokyo, Japan

    Yasuo Ohashi

  16. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan

    Kensei Tobinai

Authors
  1. Tadahiko Igarashi
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  2. Michinori Ogura
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Corresponding author

Correspondence to Tadahiko Igarashi.

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Conflict of interest

Tadahiko Igarashi and Kiyoshi Ando received research funding from Zenyaku Kogyo. Masafumi Taniwaki and Kazuhito Yamamoto received research funding from Chugai Pharmaceutical. Hirokazu Nagai received honoraria from Chugai Pharmaceutical. Yasuo Ohashi is a board member and stockholder of Statcom and received honoraria from Chugai Pharmaceutical. Kensei Tobinai received research funding from Zenyaku Kogyo and Chugai Pharmaceutical, and honoraria from Zenyaku Kogyo. The remaining authors have no conflict of interests to disclose.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s12185-016-2155-3.

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Igarashi, T., Ogura, M., Itoh, K. et al. Japanese phase II study of rituximab maintenance for untreated indolent B-cell non-Hodgkin lymphoma with high tumor burden. Int J Hematol 104, 700–708 (2016). https://doi.org/10.1007/s12185-016-2097-9

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  • DOI: https://doi.org/10.1007/s12185-016-2097-9

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