Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

Abstract (PubMed)

Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer treatment. Although rare, fulminant and fatal toxic effects may complicate these otherwise transformative therapies; characterizing these events requires integration of global data. We conducted a systematic review and meta-analysis to determine the spectrum, timing, and clinical features of fatal toxic effects associated with ICIs approved by the US FDA. We identified 613 patients with fatal ICI-associated toxic events from a global pharmacovigilance database, clinical trials, and case reports. The case fatality rate was 1.23 events per 1000 prescriptions for anti-PD-1/PD-L1 monotherapy and 1.08 for anti-CTLA-4 monotherapy, but substantially higher for combination therapy (1.59 per 1000). The most common fatal toxic effects were pneumonitis (35%), colitis (17%), hepatitis (15%), and neurologic events (15%). Most deaths occurred within 14 days of onset of the toxic event. Combination anti-PD-1/PD-L1 plus anti-CTLA-4 therapy was associated with a higher risk of fatal colitis and myocarditis compared with monotherapy.