Immune Checkpoint Inhibitor-related Pulmonary Toxicity

A Comprehensive Review, Part II

Hazim Bukamur, MD; Akram Alkrekshi, MD, PgDip; Heather Katz, DO; Mohamed Alsharedi, MD; Yousef R. Shweihat, MD; Nancy J. Munn, MD


South Med J. 2021;114(9):614-619. 

In This Article

Abstract and Introduction


The development of immune checkpoint inhibitors (ICIs) has changed the treatment paradigm for cancer. The ICIs nivolumab, pembrolizumab, and cemiplimab target programmed cell death protein 1, and durvalumab, avelumab, and atezolizumab target programmed death ligand 1. Ipilimumab targets cytotoxic T lymphocyte–associated antigen-4. Used as monotherapy or in combination, they have shown remarkable efficacy in melanoma, lung cancer, and many other solid tumors, and indications continue to evolve. These checkpoint inhibitors are typically well tolerated; however, they may cause immune-mediated adverse effects, resulting in inflammation of any organ system. Pulmonary toxicity is vital to recognize, and it can be more challenging to diagnose in patients with lung cancer, given the nature of the disease course and treatment.


In part I of this review, we discussed the pulmonary adverse events (AEs) of programmed cell death protein 1 (PD-1) inhibitor (nivolumab).[1] Here, in part II, we focus on the pulmonary AEs of PD-1 inhibitor (pembrolizumab), PD-ligand 1 (PD-L1) inhibitors (durvalumab, avelumab, and atezolizumab), and the combination of a PD-1 inhibitor (nivolumab) with a cytotoxic T lymphocyte–associated antigen 4 inhibitor (ipilimumab). These AEs include dyspnea, pneumonitis, pleural effusion, pulmonary sarcoidosis, pulmonary tuberculosis (TB), acute fibrinous organizing pneumonia (OP), OP, eosinophilic pneumonia, adult respiratory distress syndrome, and lung cavitation.

We conducted an electronic literature search for studies in the English language published in MEDLINE/PubMed from January 1, 2010 to June 30, 2019. The search terms included "pembrolizumab," "nivolumab," "atezolizumab," "durvalumab," "avelumab," "ipilimumab," interstitial lung disease," "pneumonitis," "organizing pneumonia," "eosinophilic pneumonia,", "tuberculosis," "invasive aspergillosis," "pleural effusion," "lung cavitation," and "asthma."