OncoImmunology (Jan 2020)

Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis

  • Boris Shulgin,
  • Yuri Kosinsky,
  • Andrey Omelchenko,
  • Lulu Chu,
  • Ganesh Mugundu,
  • Sergey Aksenov,
  • Rodrigo Pimentel,
  • Garrett DeYulia,
  • Geoffrey Kim,
  • Kirill Peskov,
  • Gabriel Helmlinger

DOI
https://doi.org/10.1080/2162402X.2020.1748982
Journal volume & issue
Vol. 9, no. 1

Abstract

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Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse events (AEs), which may be dependent on ICI dose. Applying a model-based meta-analysis to evaluate safety data from published clinical trials from 2005 to 2018, we analyzed the dose/exposure dependence of ICI treatment-related AE (trAE) and immune-mediated AE (imAE) rates. Unlike with PD-1 inhibitor monotherapy, CTLA-4 inhibitor monotherapy exhibited a dose/exposure dependence on most AE types evaluated. Furthermore, combination therapy with PD-1 inhibitor significantly strengthened the dependence of trAE and imAE rates on CTLA-4 inhibitor dose/exposure.

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