Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan

Blood Cancer Journal, Nov 2017

Yutaka Tsukune, Makoto Sasaki, Takeshi Odajima, Kazutaka Sunami, Tomomi Takei, Yukiyoshi Moriuchi, Masaki Iino, Atsushi Isoda, Aya Nakaya, Tsuyoshi Muta, et al.

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Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan

Tsukune et al. Blood Cancer Journal Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan Yutaka Tsukune 0 Makoto Sasaki 0 Takeshi Odajima 1 Kazutaka Sunami 10 Tomomi Takei 11 Yukiyoshi Moriuchi 12 Masaki Iino 13 Atsushi Isoda 14 Aya Nakaya 15 Tsuyoshi Muta 16 Takaaki Miyake 17 Koji Miyazaki 2 Takayuki Shimizu 3 Kei Nakajima 4 Aiko Igarashi 5 Koji Nagafuji 6 Taro Kurihara 7 Tomonori Aoyama 8 Hiroki Sugimori 9 Norio Komatsu 0 0 Department of Hematology, Juntendo University School of Medicine , Bunkyoku, Tokyo 113-8421 , Japan 1 Faculty of Health Science, Daito Bunka University, School of Sports and Health Science , Higashi-Matsuyama, Saitama 355-8501 , Japan 2 Department of Transfusion and Cell Transplantation, Kitasato University School of Medicine , Sagamihara, Kanagawa 252-0374 , Japan 3 Division of Hematology, Department of Medicine Keio University School of Medicine , Shinjuku-ku, Tokyo 160-8582 , Japan 4 Department of Hematology/Oncology, University of Yamanashi , Chuo, Yamanashi 409-3898 , Japan 5 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital , Bukyo-ku, Tokyo 113-8677 , Japan 6 Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine , Kurume, Fukuoka 830-0011 , Japan 7 Department of Internal Medicine, Niigata Cancer Center Hospital , Niigata, Niigata 951-8566 , Japan 8 Department of Gastroenterology, Juntendo University School of Medicine , Bunkyo-ku, Tokyo 113-8421 , Japan 9 Department of Preventive Medicine, Daito Bunka University, Graduate School of Sports and Health Science , Higashi-Matsuyama, Saitama 355-8501 , Japan 10 Department of Hematology, National Hospital Organization Okayama Medical Center , Okayama, Okayama 701-1192 , Japan 11 Department of Hematology, Japanese Red Cross Medical Center , Shibuya-ku, Tokyo 150-8935 , Japan 12 Department of Hematology, Sasebo City General Hospital , Sasebo 857- 0056 Nagasaki , Japan 13 Department of Hematology, Yamanashi Prefectural Central Hospital , Kofu, Yamanashi 400-8506 , Japan 14 Department of Hematology, National Hospital Organization Shibukawa Medical Center , Shibukawa, Gunma 377-0280 , Japan 15 First Department of Internal Medicine, Kansai Medical University , Hirakata, Osaka 573-1010 , Japan 16 Department of Hematology/Oncology, Japan Community Health Care Organization Kyushu Hospital , Kita-Kyusyu, Fukuoka 806-8501 , Japan 17 Department of Oncology/ Hematology, Shimane University Hospital , Izumo, Shimane 693-8501 , Japan An estimated two billion people worldwide have been infected with the hepatitis B virus (HBV). Specifically, the prevalence of HBV infection is particularly high in Asia, including Japan. HBV reactivation (HBVr) can occur in HBV carriers and in patients with resolved HBV infection who are receiving cancer chemotherapy. HBVr can induce severe flares of hepatitis and lead to fatal fulminant hepatitis. With the increasing availability of rituximabbased regimens, HBVr has become a well-known complication of lymphoma chemotherapy. However, before the era of novel agents, such as proteasome inhibitors and immunomodulatory drugs (IMiDs), there were few reports of HBVr in patients with multiple myeloma (MM). Since the approval of these novel agents, the number of reports has increased1-3. In our previous study of 641 patients with MM, we reported that 9 of 99 (9.1%) patients with resolved HBV infection experienced HBVr4. Furthermore, the cumulative incidences of HBVr at 2 and 5 years were 8% and 14%, respectively. While our previous study concluded that HBVr was not rare, reasonable risk factors were not identified4. Therefore, this nationwide retrospective study aimed to evaluate the actual incidence and risk factors of HBVr in Japanese patients with MM. - This study included patients who were diagnosed with symptomatic MM using the International Myeloma Working Group diagnostic criteria between January 2006 and February 2016 at board certified institutes of the Japanese Society of Hematology. The terminology and definitions used remain the same as in our previous report4. This study was performed in accordance with the ethical principles of the Declaration of Helsinki and was approved by the ethics review board of each participating institution. Informed consent was obtained from all patients. A multivariate logistic regression model was applied to identify independent risk factors related to HBVr using SAS statistical analysis software (version 9.4.; SAS Institute Inc., Cary, NC, USA). The other analyses were performed using the same methods as our previous report4. This study collected data from 5078 patients, including data on 641 patients evaluated in our previous study, from 76 Japanese hospitals4. All patients had been treated with either novel agents (bortezomib, thalidomide, lenalidomide, pomalidomide, panobinost (...truncated)


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Yutaka Tsukune, Makoto Sasaki, Takeshi Odajima, Kazutaka Sunami, Tomomi Takei, Yukiyoshi Moriuchi, Masaki Iino, Atsushi Isoda, Aya Nakaya, Tsuyoshi Muta, Takaaki Miyake, Koji Miyazaki, Takayuki Shimizu, Kei Nakajima, Aiko Igarashi, Koji Nagafuji, Taro Kurihara, Tomonori Aoyama, Hiroki Sugimori, Norio Komatsu. Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan, Blood Cancer Journal, 2017, Issue: 7, DOI: 10.1038/s41408-017-0002-2