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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2627-2632.
Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2004-12-4602.
 Previous Article | Table of Contents | Next Article 
CLINICAL TRIALS AND OBSERVATIONS
Humanized anti–interleukin-6 receptor antibody treatment of multicentric Castleman disease
Norihiro Nishimoto,
Yuzuru Kanakura,
Katsuyuki Aozasa,
Takeshi Johkoh,
Minoru Nakamura,
Shuji Nakano,
Nobuaki Nakano,
Yasuo Ikeda,
Takeshi Sasaki,
Kiyoshi Nishioka,
Masamichi Hara,
Hirokuni Taguchi,
Yukihiko Kimura,
Yoshiro Kato,
Hideki Asaoku,
Shunichi Kumagai,
Fumio Kodama,
Hideko Nakahara,
Keisuke Hagihara,
Kazuyuki Yoshizaki, and
Tadamitsu Kishimoto
From Osaka University, Osaka; Kyowakai Hospital, Osaka; Kyushu University, Fukuoka; Keio University, Tokyo; Tohoku University, Miyagi; Tokyo Medical and Dental University, Tokyo; Ehime Prefectural Central Hospital, Ehime; Kochi Medical School, Kochi; Tokyo Medical University, Tokyo; Aichi Medical University, Aichi; Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima; Kobe University, Hyogo; and Kanagawa Cancer Center, Kanagawa, Japan; as the Japanese MRA study group on MCD.
Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti–human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.
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