Pretreatment serum level of interleukin-6 predicts carfilzomib-induced hypertension in relapsed/refractory multiple myeloma

Abstract

Carfilzomib (CFZ) constitutes powerful combinatory therapy for relapsed/refractory multiple myeloma (RRMM); however, cardiovascular adverse events (CVAEs) have been shown as major treatment obstacles with the use of CFZ. Along with our multi-institutional prospective observational study by the Kyoto Clinical Hematology Study Group on the efficacy and safety of CFZ-based treatments (UMIN000025108), we here performed an ad hoc analysis of CFZ-related CVAEs in 50 patients with RRMM. We analyzed the association between CFZ-related CVAEs and pre-planned examinations, including patients’ background, electrocardiographic findings, echocardiographic findings, and serum/plasma levels of 18 potential candidate biomarkers. The common CVAEs were hypertension (42%), arrhythmia (14%), and prolongation of QT corrected interval (10%), whereas no serious CVAEs occurred. The pretreatment serum level of interleukin-6 was identified as a significant risk factor for CFZ-related hypertension. This study revealed hypertension as the most frequent CFZ-related CVAE and suggested that baseline serum interleukin-6 is a useful predictor for CFZ-induced hypertension.

Keywords:

• Cardiovascular adverse events
• carfilzomib
• hypertension
• interleukin-6
• multiple myeloma

Acknowledgements

We thank all patients and their families for enrolling in this study. Furthermore, we thank all researchers in the Kyoto Clinical Hematology Study Group for their scientific support.

Ethical approval

This study was conducted in compliance with the Guidelines for Good Clinical Practice and the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Boards of individual institutions. All patients provided written informed consent before participation in the study.

Author contributions

J.K., T.K., and A.M. analyzed and interpreted the data. J.K. and T.K. were involved in the study conception and design. A.M., Y.K., H.U, N.S., N.U., M.N., R.T., K.S., H.K., M.K., K.W., Y.C., K.H., S.F., C.S., Y.M., S.M., T.T., Y.S., S.H., and M.T. were involved in data acquisition. T.K. and A.M. performed statistical analyses and S.T. provided statistical advice. A.M. drafted the manuscript. J.K. and T.K. helped revise the manuscript. All authors read and approved the final manuscript.

Disclosure statement

J.K. is a consultant of Janssen Pharmaceutical K.K, Celgene, Bristol-Myers Squibb, Sanofi, and Abbvie. Others have no conflicts of interest to declare. J.K. has received research funding from Bristol–Myers Squibb, Sysmex, Celgene, Ono Pharmaceutical, Otsuka Pharmaceutical, Sanofi, Kyowa Kirin, Sanofi, Chugai Pharmaceutical, Eisai, Dainippon Sumitomo Pharma, Nippon Shinyaku, Takeda, Shionogi, Asahi Kasei, Daiichi Sankyo, MSD, Taiho Pharmaceutical, and Abbvie; has received honoraria from Bristol–Myers Squibb, Janssen Pharmaceutical K.K, Celgene Corporation, Ono Pharmaceutical, Takeda, Sanofi, Kyowa Kirin, Chugai Pharmaceutical, Eisai, Astellas Pharma, Nippon Shinyaku, Dainippon Sumitomo Pharma, Symbio, Daiichi Sankyo, Fujimoto Pharmaceutical, Abbvie, and Otsuka Pharmaceutical. T.K. has received honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, Eisai, and Nippon Shinyaku. T.T. has received research funding from Nippon Shinyaku. S.T. has received research funding from Nippon Boehringer Ingelheim; has received honoraria from Daiichi Sankyo, Sanofi, Takeda Pharmaceutical, Bayer, Sysmex, Chugai Pharmaceutical, Solasia Pharma, Nipro, NapaJen Pharma, Gunze, and Kringle Pharma.

Additional information

Funding

This work was funded by Ono Pharmaceutical Co., Ltd.