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Observational Study
. 2022 Apr 28;17(4):e0267572.
doi: 10.1371/journal.pone.0267572. eCollection 2022.

Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse events

Machiko Kawahira  1 , Shuji Kanmura  1 , Keiko Mizuno  2 , Kentaro Machida  2 , Takao Ohtsuka  3 , Masami Sato  4 , Hideki Enokida  5 , Masaru Yamashita  6 , Takuro Kanekura  7 , Shiho Arima  1 , Norifumi Nakamura  8 , Tsuyoshi Sugiura  9 , Koji Yoshimoto  10 , Hiroaki Kobayashi  11 , Kenji Ishitsuka  12 , Shinsuke Suzuki  13 , Shinichi Ueno  13 , Akio Ido  1
Affiliations
Observational Study

Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse events

Machiko Kawahira et al. PLoS One. .

Abstract

Background and aims: Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach.

Methods: In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed.

Results: Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group.

Conclusions: Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

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Conflict of interest statement

Dr. Ishitsuka holds has received a research fund from ONO PHARMACEUTICAL CO., LTD. The remaining authors have no financial relationships to disclose that are relevant to this publication.

Figures

Fig 1
Fig 1. Participants in this study.
ICI: immune checkpoint inhibitors, irAE: immune-related adverse event.
Fig 2
Fig 2. Flow diagram of irAE resumption.
ICI: immune checkpoint inhibitors, irAE: immune-related adverse event.
See this image and copyright information in PMC

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