Cancer immunotherapy: checkpoint inhibitors, CAR T cells and immune-related toxicity

At a glance

• Checkpoint inhibitors are monoclonal antibodies that remove brakes on T cells: anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab, cemiplimab), anti-PD-L1 (atezolizumab, durvalumab, avelumab) and anti-LAG-3 (relatlimab, combined with nivolumab).
• The same loss of tolerance that kills tumour causes immune-related adverse events (irAEs) in skin, gut, liver, endocrine glands, lung and, rarely, heart and nerve.
• Combination ipilimumab plus nivolumab has the highest toxicity: grade 3 to 4 events in about 55 to 60% of patients in CheckMate 067, against roughly 15 to 20% with PD-1 monotherapy.