Pulmonary adverse events following immune checkpoint inhibitors

Abstract

Purpose of reviewImmune checkpoint inhibitors (ICIs) have rapidly become a mainstay of cancer treatment. However, immune modulation resulting from checkpoint inhibition can cause inflammation in any organ system, with pneumonitis being one of the most severe immune-related adverse events (irAEs). Here, we review the most recent literature on pulmonary adverse events following ICIs.Recent findingsSeveral systematic reviews and meta-analyses of data from trials of antiprogrammed death-1 (PD-1; nivolumab, pembrolizumab), anti-PD-ligand-1 (PD-L1; atezolizumab, avelumab, durvalumab) and anticytotoxic T lymphocyte antigen-4 (CTLA-4; ipilimumab or tremelimumab) in patients with advanced cancer have explored the relative risk and incidence of lung toxicity among different tumor types and therapeutic regimens. They have showed that the incidence of all-grade (1–4) and high-grade (3–4) pneumonitis is significantly higher in nonsmall cell lung cancer (NSCLC) compared with other tumor types. In addition, they have demonstrated that immunotherapy, especially monoimmunotherapy, has a significantly lower risk of irAEs compared to immune-chemotherapy. Treatment for lung cancer, preexisting interstitial lung disease, smoking history and male sex appear to increase the risk for ICI-related pneumonitis.SummaryLung toxicity is an uncommon but potentially severe and even fatal complication of ICIs. Timely recognition is critically important but challenging, particularly in patients with lung cancer wherein drug toxicity can mimic disease progression or recurrence.

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma

“…Interstitial pneumonia occurred in two patients and led to treatment discontinuation in both patients. The complications of interstitial pneumonia can be severe, demonstrating the need for caution 17 . Proteinuria with grade ≥2 was observed in 26 patients and resulted in treatment discontinuation in six of these patients.…”

Immune Checkpoint Inhibitors: A Narrative Review on PD-1/PD-L1 Blockade Mechanism, Efficacy, and Safety Profile in Treating Malignancy

“…Several other factors can contribute to a patient being more susceptible to developing pneumonitis during treatment. These factors include underlying interstitial lung disease, male sex, and significant smoking history [69].…”

“…Several other factors can contribute to a patient being more susceptible to developing pneumonitis during treatment. These factors include underlying interstitial lung disease, male sex, and significant smoking history [ 69 ]. Treating drug-induced pneumonitis typically involves completely withdrawing or temporarily delaying immunotherapy.…”

Management of patients with idiopathic pulmonary fibrosis and lung cancer: challenges in clinical practice

“…On the other hand, pneumonitis in patients with IPF might be fatal [42,91]. Lower doses might be the key to target PD-1/PD-L1 axis, which seems to have a role in lung fibrosis as well, and concomitantly reduce the likelihood of adverse events [95][96][97][98][99][100][101]. Multidisciplinary discussion for the risk-benefit ratio on a case-by-case basis is suggested.…”