The knowns & unknowns of pulmonary toxicity following immune checkpoint inhibitor therapies: a narrative review

Since their discovery immune checkpoint inhibitors (ICI) have dramatically changed the treatment landscape for many cancers. In addition to their efficacy they are generally well tolerated, however, they have led to a new range of immune-related adverse events (irAEs) including pneumonitis. While not the most frequently reported immune-related adverse event in the clinical trial setting, recent real-world data suggests a significantly higher rate of pneumonitis leading to treatment suspension or cessation. It also appears to disproportionately contribute to immune-related mortality, particularly with anti-PD-1/PD-L1 treatment. While indicators have emerged regarding risk factors, incomplete prospective recording of patient characteristics hampers strong conclusions. Presenting symptoms are non-specific and the differential diagnosis is broad, made more complex by concomitant treatment with traditional chemotherapy or radiotherapy. Radiological findings are diverse and inconsistent terminology makes comparison and more complete characterization difficult. Further, little is known about the role of baseline testing or surveillance for early detection of pneumonitis, or the real-world role of bronchoscopy or biopsy in assessment. Scant literature exists to direct these complex decisions, so treatment guidelines have been published based on expert consensus. Here we provide a narrative review of what is known about ICI pneumonitis and propose key questions to enhance our understanding into the future.