Clinicopathologic characteristics of 342 patients with multicentric Castleman disease in Japan

Abstract

Objectives: To assess the clinicopathologic features of Multicentric Castleman disease (MCD) patients in Japan.

Methods: We assessed baseline data for 342 Japanese MCD patients with a biopsy-proven diagnosis, enrolled in a prospective, observational study for tocilizumab treatment.

Results: Of 342 patients, 86.0% had plasma-cell type. None had a family history of MCD. Median disease duration of MCD was 3.7 years. Mean body weight and body mass index tended to be lower than those in the general Japanese population. The most common clinical presentations besides lymphadenopathy included fatigue (61.7%), pulmonary involvement (42.7%), and splenomegaly (41.8%). Secondary amyloidosis was reported in 34 patients (9.9%). Laboratory abnormalities included decreased hemoglobin and albumin, and increased acute-phase proteins, serum immunoglobulins, and interleukin-6 (IL-6). IL-6 levels among the MCD patients tested in this study were correlated with levels of albumin, hemoglobin, triglyceride, total cholesterol, C-reactive protein, fibrinogen and immunoglobulin G (Spearman’s correlation coefficient, |r| = 0.28–0.59).

Conclusion: The clinical features and laboratory abnormalities are similar to those previously reported in other countries, besides higher rates of pulmonary involvement, secondary amyloidosis, and ECG abnormalities. Our results imply that IL-6 is involved in MCD pathogenesis. These findings would be informative for diagnosis and appropriate treatment for MCD.

Keywords:

• IL-6
• inflammation
• multicentric Castleman disease
• real-world data

Acknowledgments

The authors thank all our patients, their families, and the physicians who participated in this study. The authors thank the late Dr. Junichi Azuma for his influential leadership in the Safety Evaluation Committee of tocilizumab for Castleman disease. The authors thank Dr. Misato Hashizume for drafting the manuscript. The academic authors vouch for the completeness and accuracy of the data and data analyses, and for the fidelity of the study to the protocol.

Authorship

All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. NN contributed study concept. TJ, SH, SO, M Mizuki, SN and NN contributed study design and protocol. TJ, SH, SO, M Mizuki, SN and NN contributed data collection and enrollment. M Murakami, TJ, SH, SO, M Mizuki, SN, MT, KK, AN and NN analyzed or interpreted data. M Murakami, MT, KK, AN and NN drafted the manuscript; All authors revised the manuscript.

Conflict of interest

M. Murakami has received personal fees from Chugai Pharmaceutical, grants from Chugai Pharmaceutical, AYUMI Pharmaceutical, and Sekisui medical, grants and personal fees from Eisai, grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. TJ has nothing to disclose. SH has received personal fees from Chugai pharmaceutical. SO has received speakers bureau fees, or consulting fees from Chugai, Bristol-Myers Squibb, AbbVie, Astellas, Takeda, Tanabe-Mitsubishi, Daiichi-Sankyo and Janssen. M Mizuki has received personal fees from Chugai Pharmaceutical, and Takeda. SN has nothing to disclose. MT, KK, and AN are employees of Chugai Pharmaceutical. NN has received grants and personal fees from Chugai Pharmaceutical, Eisai, Sekisui medical and AYUMI Pharmaceutical; personal fees from Mitsubishi Tanabe, Pfizer, AbbVie, UCB Japan, Novartis, and grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.