Need for aligning the definition and reporting of cytokine release syndrome (CRS) in immuno-oncology clinical trials

Abstract

As cancer immunotherapies continue to expand across all areas of oncology, it is imperative to establish a standardized approach for defining and capturing clinically important toxicities, such as cytokine release syndrome (CRS). In this paper, we provide considerations for categorizing the variety of adverse events that may accompany CRS and for recognizing that presentations of CRS may differ among various immunotherapies (e.g., monoclonal antibodies, CAR T cell therapies and T cell engagers, which can include bispecific antibodies and other constructs). The goals of this paper are to ensure accurate and consistent identification of CRS in patients receiving immunotherapies in clinical studies to aid in reporting; enable more precise evaluation of the therapeutic risk-benefit profile and cross-study analyses; support evidence-based monitoring and management of important toxicities related to cancer immunotherapies; and improve patient care and outcomes. These efforts will become more important as the number and variety of molecular targets for immunotherapies broaden and as therapies with novel mechanisms continue to be developed.

Keywords: Cytokine Release Syndrome (CRS); Drug development; Immunotherapies; T cell receptors.

Figure 1.

Decision tree for assessing a population-level CRS risk during product development of an experimental agent. A decision tree approach to characterizing the safety profiles of new molecules during preclinical and early clinical development. This process would begin with an initial assessment of the molecule’s potential for CRS or IRR, based on preclinical data, mechanism of action and experience with other agents in the same therapeutic class.

Figure 2.

Patient treatment timeline and event reporting after immunotherapy administration.