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Efficacy and safety of obinutuzumab in patients with previously untreated follicular lymphoma: a subgroup analysis of patients enrolled in Japan in the randomized phase III GALLIUM trial

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Abstract

GALLIUM is a global phase III study that demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with obinutuzumab plus chemotherapy (G-chemo) versus rituximab plus chemotherapy (R-chemo) in previously untreated patients with follicular lymphoma (FL). In this single-country subgroup analysis, we explored patterns of efficacy and safety in patients enrolled in the GALLIUM study in Japan (Japanese subgroup). Patients were randomized to open-label induction treatment with G-chemo or R-chemo. Responders received maintenance monotherapy with their randomized antibody for up to 2 years. The primary endpoint was investigator-assessed PFS. Overall, 123 patients with FL were randomized in the Japanese subgroup (G-chemo, n = 65; R-chemo, n = 58). The majority of patients received cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (82.9 vs 33.1% in the global GALLIUM FL population). PFS at 3 years was 89.9% (G-chemo) vs. 74.7% (R-chemo); hazard ratio 0.42; 95% confidence interval 0.15, 1.15; P = 0.08. Higher rates of grade 3–5 adverse events (96.9 vs. 89.7%) and serious adverse events (35.4 vs. 22.4%) were observed with G-chemo vs R-chemo, respectively. Neutropenia was frequent in the Japanese subgroup (92.3% G-chemo; 79.3% R-chemo). Overall, the results in the Japanese subgroup were consistent with those in the global GALLIUM population.

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Acknowledgements

The authors would like to thank the UK and German study groups (UK National Cancer Research Institute, German Low Grade Lymphoma Study Group and the East German Study Group Hematology and Oncology) for their scientific support of the GALLIUM study, all of the GALLIUM study investigators, their teams, and the patients for their participation. The GALLIUM trial was sponsored by F. Hoffmann-La Roche Ltd. Medical writing support for this article was provided by Lynda McEvoy, PhD (Gardiner-Caldwell Communications, Macclesfield, UK), funded by Chugai Pharmaceutical Co Ltd.

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Authors and Affiliations

  1. School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, Japan

    Ken Ohmachi & Kiyoshi Ando

  2. National Cancer Center Hospital, Tokyo, Japan

    Kensei Tobinai

  3. Aichi Cancer Center, Nagoya, Aichi, Japan

    Tomohiro Kinoshita

  4. Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan

    Takayuki Ishikawa

  5. The Cancer Institute Hospital, Tokyo, Japan

    Kiyohiko Hatake

  6. Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Satoshi Ichikawa

  7. Jichi Medical University, Shimotsuke, Tochigi, Japan

    Ken Ohmine

  8. Matsushita Memorial Hospital, Moriguchi, Osaka, Japan

    Yuri Kamitsuji

  9. National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Ilseung Choi

  10. Niigata Cancer Center Hospital, Niigata, Japan

    Takaaki Chou

  11. National Cancer Center Hospital East, Chiba, Japan

    Kunihiro Tsukasaki

  12. Chiba Cancer Center, Chiba, Japan

    Kyoya Kumagai

  13. Kyoto Prefectural University of Medicine, Kyoto, Japan

    Masafumi Taniwaki

  14. Japanese Red Cross Nagoya Daini Hospital, Nagoya, Aichi, Japan

    Toshiki Uchida

  15. Kumamoto University Graduate School of Medicine, Kumamoto, Japan

    Yoshitaka Kikukawa

  16. Aomori Prefectural Central Hospital, Aomori, Japan

    Kohmei Kubo

  17. Hiroshima University Hospital, Hiroshima, Japan

    Keichiro Mihara

  18. Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Norifumi Tsukamoto

  19. Toranomon Hospital, Tokyo, Japan

    Koji Izutsu

  20. National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan

    Isao Yoshida

  21. Shinshu University School of Medicine, Nagano, Japan

    Fumihiro Ishida

  22. The Jikei University School of Medicine, Tokyo, Japan

    Noriko Usui

  23. Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan

    Shinsuke Iida

  24. Hyogo Cancer Center, Akashi, Hyogo, Japan

    Tohru Murayama

  25. Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

    Eisuke Ueda & Hiroshi Kuriki

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  1. Ken Ohmachi
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  2. Kensei Tobinai
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  7. Ken Ohmine
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Correspondence to Ken Ohmachi.

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Conflict of interest

KO reports personal fees from Chugai Pharmaceutical Co Ltd, Kyowa Hakko Kirin Co Ltd, Eisai Co Ltd, Pfizer Inc and Takeda Pharmaceutical Co Ltd. KT reports Grants and personal fees from Chugai Pharmaceutical Co Ltd/Roche, Celgene, Eisai, Janssen Pharmaceuticals, Kyowa Hakko Kirin, Mundipharma, Ono Pharmaceutical and Takeda; Grants from Abbvie, GlaxoSmithKine and Servier; and personal fees from HUYA Bioscience and Zenyaku Kogyo. TK reports Grants and personal fees from Chugai Pharmaceutical Co Ltd, Ono, Gilead, MSD and Zenyaku; Grants from Takeda and Solaisia; and personal fees from Bristol, Kyowa Kirin, Eisai and Janssen. TI, KKumagai, SI, YK, IC, TC, YK, KKubo, KM and NT report no conflicts of interest. KH reports Grants from Chugai Pharmaceutical Co. KO reports Grants and personal fees from Chugai Pharmaceutical Co Ltd and Takara-Bio Inc; and personal fees from Kyowa Hakko Kirin Co Ltd, Ono Pharmaceutical Co Ltd, Bristol-Meyers Squibb, Chugai Pharmaceutical Co Ltd and Alexion Pharmaceuticals Inc. KT reports Grants from Chugai Pharmaceutical Co Ltd, Celgene, Takeda and Mundipharma; consultancy from Huya and Ono Pharma, and lecture fees from Zenyaku Kogyo, Celgene, Huya, Kyowa Hakko Kirin and Chugai Pharmaceutical Co Ltd. MT reports Grants and personal fees from Chugai/Roche, Celgene, BMS, and Janssen Pharmaceuticals; Grants from Kyowa Hakko Kirin; and personal fees from Mundipharma. TU reports personal fees from Janssen Pharmaceuticals, Mundipharma, Celgene, Teijin, Novartis, Nippon Shinyaku, Pfizer, Briston-Myers Squibb, and Meiji Seika Pharama. KI reports Grants from Kenyaku Kogyo, Mundhi, Abbvie, Solasia, Celltrion, Symbio, Astellas, Astellas Amgen, Novartis and Sanofi; Grants and personal fees from Takeda, Eisai, Chugai Pharmaceutical Co Ltd, Gilead, Janssen, Ono, Celgene, MSD, Bayer and Daiichi-Sankyo, personal fees from Kyowa Hakko Kirin; and discloses a relationship with HUYA Bioscience International. IY reports research funding and honoraria from Kyowa Hakko Kirin; research funding from Chugai; and honoraria from Celgene. FI reports Grants and personal fees from Chugai Pharmaceutical Co Ltd, Kyowa Hakko Kirin, and Takeda; Grants from Bristol-Myers-Squibb; and personal fees from Celgene. NU reports research Grants from AMED, Pfizer Co, Sysmex Co, Kyowa Hakko Kirin Co, Bristol-Myers-Squibb, Novartis, Nippon Shinyaku, Fujimoto and Celgene; payment for data monitoring committee membership from CIMIC Co, Takeda Bio Development Center, Lilly Japan, Pfizer Co, Nippon Boehringer-Ingelheim Co, Janssen Pharmaceutical Co, Zenyaku Kogyo Co, Kyowa Hakko Kirin Co, Otsuka Pharm Co, Celgene Co, SymBio Pharmaceutical Co, Huya Bioscience International, and Astellas Pharmaceutical Co; and payment for speaker’s bureau for Chugai Pharmaceutical Co Ltd and Bristol-Myers-Squibb. SI reports Grants from Chugai Pharmaceutical Co Ltd, Kyowa Hakko Kirin, Astellas, Toyama Chemicals, Teijin Pharma, Sanofi, Bayer, J-Pharma, Eli Lilly, and Daiichi Sankyo; and Grants and personal fees from Ono, Janssen, Celgene, Bristol-Myers-Squibb, Novartis, and Takeda. TM reports personal fees from Bristol-Myers-Squibb, Celgene, Esai, Janssen Pharmaceutical, Kyowa Hakko Kirin, Nippon Shinyaku, Novartis, Ono Pharmaceuticals, Otsuka Pharmaceuticals, Pfizer, Sanofi, Siemens Healthcare Diagnostics, Sumitomo Dainippon Pharma, and Taiho Pharmaceutical. EU and HK are employees of Chugai Pharmaceutical Co Ltd. HK reports stock ownership for Chugai Pharmaceutical Co Ltd. KA reports subsidies or donations from Meiji Seika Pharma Co Ltd, Takeda Pharmaceutical Co Ltd, Eizai Co Ltd, Kyowa Kirin and the Japan Blood Products Organization.

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Ohmachi, K., Tobinai, K., Kinoshita, T. et al. Efficacy and safety of obinutuzumab in patients with previously untreated follicular lymphoma: a subgroup analysis of patients enrolled in Japan in the randomized phase III GALLIUM trial. Int J Hematol 108, 499–509 (2018). https://doi.org/10.1007/s12185-018-2497-0

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