PLoS ONE (Jan 2022)

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

  • Machiko Kawahira,
  • Shuji Kanmura,
  • Keiko Mizuno,
  • Kentaro Machida,
  • Takao Ohtsuka,
  • Masami Sato,
  • Hideki Enokida,
  • Masaru Yamashita,
  • Takuro Kanekura,
  • Shiho Arima,
  • Norifumi Nakamura,
  • Tsuyoshi Sugiura,
  • Koji Yoshimoto,
  • Hiroaki Kobayashi,
  • Kenji Ishitsuka,
  • Shinsuke Suzuki,
  • Shinichi Ueno,
  • Akio Ido

DOI
https://doi.org/10.1371/journal.pone.0267572
Journal volume & issue
Vol. 17, no. 4
p. e0267572

Abstract

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Background and aimsImmune 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.MethodsIn 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.ResultsTwo-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.ConclusionsPatients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.