Diagnostic and therapeutic approach to pulmonary infiltrates in cancer patients receiving immune checkpoint inhibitors

Abstract

The advent of immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death (PD-1)/PD-1 ligand 1 (PD-L1) axis has transformed the treatment paradigm for multiple cancer types. ICIs are able to restore T-cell-mediated antitumor responses and do not entail an increased risk of infection per se. However, immunotherapy is associated to a unique form of toxicity due to the off-target effects on healthy tissues of the excessively enhanced immune response in form of immune-related adverse events (irAEs). Although ICI-induced pneumonitis ranks the fifth of all irAEs in terms of frequency of occurrence, it is associated with a relevant attributable mortality. This review summarizes the incidence, risk factors, clinical and radiological presentation, and therapeutic approach of ICI-induced pneumonitis. Particular focus is on the differential diagnosis of new or worsening pulmonary infiltrates in cancer patients receiving ICI therapy. Finally, the impact on the risk of opportunistic infection of ICIs and immunosuppressive therapy used to treat associated irAEs is reviewed. The diagnosis and management of suspected ICI-induced pneumonitis remains clinically challenging.