Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jul 24, 2022; 13(7): 641-651
Published online Jul 24, 2022. doi: 10.5306/wjco.v13.i7.641
Necessity of neutrophil-to-lymphocyte ratio monitoring for hypothyroidism using nivolumab in patients with cancer
Ako Gannichida, Yusuke Nakazawa, Akira Kageyama, Hirofumi Utsumi, Kazuyoshi Kuwano, Takashi Kawakubo
Ako Gannichida, Yusuke Nakazawa, Akira Kageyama, Takashi Kawakubo, Department of Pharmacy, The Jikei University Hospital, Tokyo 105-8471, Japan
Hirofumi Utsumi, Kazuyoshi Kuwano, Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan
Author contributions: Gannichida A drafted the article and collected the data; Nakazawa Y designed the research; Nakazawa Y and Kageyama A analyzed and interpreted the data; Utsumi H and Kuwano K provided clinical advice; Nakazawa Y, Kageyama A, Utsumi H, Kuwano K, and Kawakubo T contributed to the critical revision of the article for important intellectual content; Kawakubo T provided the final approval for this article.
Institutional review board statement: The study protocol was approved by the Ethics Committee of the Jikei University [No. 31-048 (9547)].
Informed consent statement: This study was a retrospective observational study conducted using the opt-out method. Informed consent for the study was not required because the analysis used anonymous clinical data obtained after each patient had agreed to treatment through written consent. For full disclosure, the details of the study were mentioned in the opt-out document in the Jikei University School of Medicine.
Conflict-of-interest statement: Kazuyoshi Kuwano received study support from Ono Pharmaceutical Co., Ltd., Astellas Pharma Inc., Kyorin Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. These companies did not have a role in conducting this study. All authors have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yusuke Nakazawa, MDS, Assistant Lecturer, Department of Pharmacy, The Jikei University Hospital, 3-19-18 Nishi Shimbashi, Minato-ku, Tokyo 105-8471, Japan.
Received: February 5, 2022
Peer-review started: February 5, 2022
First decision: May 12, 2022
Revised: June 1, 2022
Accepted: June 21, 2022
Article in press: June 21, 2022
Published online: July 24, 2022
Research background

The activation of immunocompetent cells by nivolumab exerts an antitumor effect. However, excessive immune responses developed in autologous organs along with the breakdown of self-tolerance causes immune-related adverse events (irAEs), such as hypothyroidism.

Research motivation

Low neutrophil-to-lymphocyte ratio (NLR) values have been shown to be associated with a favorable therapeutic response to nivolumab. The possibility that NLR is associated with immune response implies that NLR can be not only a predictive factor for good response to nivolumab but also a predictive factor for the development of hypothyroidism.

Research objectives

To evaluate whether continuous monitoring of NLRs during nivolumab treatment is useful for predicting the incidence and onset period of hypothyroidism.

Research methods

NLR of patients who received nivolumab treatment was measured before each administration. NLR at treatment initiation was compared between patients with and without hypothyroidism during the treatment period. Patients who developed hypothyroidism were categorized into three groups as those with NLR < 3.5, NLR 3.5 to < 5, and NLR ≥ 5 according to their maximum NLR from treatment initiation to hypothyroidism development, and the onset periods of hypothyroidism were compared.

Research results

Patients with hypothyroidism showed significantly lower NLR at treatment initiation, and the incidence of hypothyroidism was higher among those with NLR < 5. Patients with persistently low NLR (< 3.5) developed hypothyroidism earlier than those with NLR 3.5 to < 5 and NLR ≥ 5.

Research conclusions

Low NLR at treatment initiation increases the incidence of treatment-induced hypothyroidism. Moreover, its persistence may be a risk factor for the early onset of hypothyroidism.

Research perspectives

The follow-up period in this study was limited to the 12th dose of nivolumab. The incidence of hypothyroidism should be evaluated throughout the treatment period.