Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors
- Study type
- Meta-analysis
- Design
- Systematic review and meta-analysis, with a retrospective analysis of the WHO pharmacovigilance database (Vigilyze) and a retrospective review of records from 7 academic centres
- Sample size
- 613 fatal toxic events in Vigilyze; 3545 patients from 7 academic centres; meta-analysis of 112 trials including 19,217 patients
- Source
- JAMA Oncol · 2018
In plain words
Immunotherapy drugs (immune checkpoint inhibitors) are important cancer treatments, but in rare cases they can cause severe and even fatal side effects. In this study, which looked at a large amount of data, death from side effects of these drugs was rare (less than 2% in clinical trials) and usually happened in the first weeks of treatment. The risk was higher with combination treatment and anti-CTLA-4 drugs than with anti-PD-1 or anti-PD-L1 drugs. If you develop new or troubling symptoms during treatment, tell your treatment team straight away.
Key results
Treatment arms and regimens
Ipilimumab or tremelimumab. Dosing details in the full text.
Nivolumab or pembrolizumab. Dosing details in the full text.
Atezolizumab, avelumab or durvalumab. Dosing details in the full text.
Dosing details in the full text.
Source of the regimen details: Abstract of the paper (drug doses are not given in the abstract)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with cancer treated with immune checkpoint inhibitors (ICIs). Data sources included the WHO pharmacovigilance database (Vigilyze) with more than 16,000,000 adverse drug reaction reports, records from 7 academic centres and published international ICI trials. Details of inclusion criteria are not given in the abstract.
Endpoints
Main outcomes: timing, spectrum, outcomes and incidence of ICI-related toxic effects.
Safety and side effects
This study itself focuses on fatal ICI toxicities. Colitis in the anti-CTLA-4 group, and pneumonitis, hepatitis and neurological events in the anti-PD-1/PD-L1 group were the most common causes of death. With combination therapy, colitis and myocarditis accounted for the largest share. Myocarditis had the highest fatality rate (39.7%).
Clinical significance and place in guidelines
This study shows that fatal ICI toxicities are rare but occur early after starting treatment, and that their causes vary by regimen. According to the abstract, physicians of all specialties should be aware of these toxicities. Myocarditis had the highest fatality rate, and combination therapy and anti-CTLA-4 were associated with higher death rates than anti-PD-1/PD-L1. Detailed recommendations for monitoring and managing toxicities should be taken from current authoritative guidelines; the abstract does not state guideline status. Note: an erratum has been published for this article and should be checked in the full text.
Limitations
Part of the data is retrospective and drawn from spontaneous pharmacovigilance reports, which may be incomplete or subject to reporting bias (this is inferred from the nature of the design and not stated explicitly in the abstract). Cancer types and drug doses are not specified in the abstract. An erratum has been published for this article.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.