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. 2021 Jul;9(7):e002896.
doi: 10.1136/jitc-2021-002896.

Immune-related adverse events associated with immune checkpoint inhibitors: a call to action for collecting and sharing clinical trial and real-world data

Kerry L Reynolds  1 , Shaily Arora  2 , Ravikumar Komandur Elayavilli  3 , William C Louv  4 , Teilo H Schaller  3 , Aakanksha Khandelwal  5 , Mace Rothenberg  6 , Sean Khozin  7 , Amanda C Guidon  8 , Michael Dougan  9 , Leyre Zubiri  10 , Laura Petrillo  11 , Meghan E Sise  12 , Alexandra-Chloe Villani  13 , Douglas B Johnson  14 , Osama Rahma  15 , Elad Sharon  16
Affiliations

Immune-related adverse events associated with immune checkpoint inhibitors: a call to action for collecting and sharing clinical trial and real-world data

Kerry L Reynolds et al. J Immunother Cancer. 2021 Jul.

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, improving outcomes in patients with advanced malignancies. The use of ICIs in clinical practice, and the number of ICI clinical trials, are rapidly increasing. The use of ICIs in combination with other forms of cancer therapy, such as chemotherapy, radiotherapy, or targeted therapy, is also expanding. However, immune-related adverse events (irAEs) can be serious in up to a third of patients. Critical questions remain surrounding the characteristics and outcomes of irAEs, and how they may affect the overall risk-benefit relationship for combination therapies. This article proposes a framework for irAE classification and reporting, and identifies limitations in the capture and sharing of data on irAEs from current clinical trial and real-world data. We outline key gaps and suggestions for clinicians, clinical investigators, drug sponsors, patients, and other stakeholders to make these critical data more available to researchers for pooled analysis, to advance contemporary understanding of irAEs, and ultimately improve the efficacy of ICIs.

Keywords: guidelines as topic; immune tolerance; immunotherapy; translational medical research; tumor biomarkers.

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Conflict of interest statement

Competing interests: KLR receives support from Teladoc and Project Data Sphere. MR owns shares of Pfizer Inc. ACG has served on advisory boards/consulted with Alexion, RA Pharma (UCB), and Momenta (Jansen). She also receives support from Project Data Sphere. MD has received support from Novartis, Eli Lilly, Moderna, Tillotts Pharma, ORIC Pharmaceuticals, and Partner Therapeutics. He is engaged with Moderna and Neoleukin Therapeutics. LZ has received support from Merck US. DBJ has received support from BMS and Incyte and serves on advisory boards for Array Biopharma, BMS, Catalyst, Iovance, Jansen, Merck, Novartis, and Oncosec. OR has received support from Merck, Celgene, Five Prime, GSK, Bayer, Roche, Puretech, Imvacx, and Sobi, has an immunotherapy patent pending, and serves as CMO of Outcomes4me.

Figures

Figure 1
Figure 1
Timeline depicting the year and indications for which immune checkpoint inhibitors were granted approval by the US Food and Drug Administration. dMMR, deficient MisMatch Repair; MSI-H, high levels of microsatellite instability; NSCLC, non-small cell lung cancer; PMBCL, primary mediastinal large B-cell lymphoma; SCLC, small cell lung cancer; TMB, tumor mutational burden.
Figure 2
Figure 2
Overview of major immune-related adverse events that have been reported according to organ system.
Figure 3
Figure 3
Stakeholders in multiple sectors, including academic, industry, and regulatory agencies, could help strengthen immune-related adverse event (irAE) data by convening task forces to standardize irAE definitions and reporting in clinical trials and develop technological tools to support real-world irAE reporting. AE, adverse event; CRF, case report forms; EHR, electronic health records.
See this image and copyright information in PMC

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