Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: Focus on Nivolumab

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


South Med J. 2020;113(11):600-605. 

In This Article

Nivolumab-related Interstitial Lung Disease

Nivolumab-related interstitial lung disease (ILD) was described in Japanese patients with recurrent or advanced non-small-cell lung cancer (NSCLC) by Kato et al[3] in two phase II studies (ONO-4538-05 and ONO-4538-06). Eight of 111 patients included in these two studies developed ILD, with a median number of 3 nivolumab doses administered before the onset of ILD. Four of these 8 patients had grade 3 or higher toxicity and were considered to have a serious treatment-related adverse event. All of the patients who had ILD were male and had a history of smoking. The median age was 65 years. ILD was rapidly resolving or resolved with steroids in 7 of the 8 patients, and their computed tomography (CT) scan showed organizing pneumonia (OP) or nonspecific interstitial pneumonia (NSIP) without traction bronchiectasis. One patient who was started on docetaxel after severe ILD toxicity due to nivolumab died of respiratory failure, with the CT scan showing traction bronchiectasis.[3]

Nakahama et al[4] reported 119 stage IV NSCLC patients treated with nivolumab between December 2015 and July 2016. Seven patients had signs of lung obstruction caused by tumor-mediated compression, which was demonstrated on imaging performed at the initiation of nivolumab treatment. These patients developed ILD, which progressed rapidly in 3 of 7 patients (43%). ILD occurred in only 12 patients (11%) among 112 who did not show signs of lung obstruction. In this study, the authors suggested that obstructive findings are more likely to be important risk factors for ILD than previous radiation therapy.[4] Two phase III trials, CheckMate 017[5] and CheckMate 057,[6] also described nivolumab-related pneumonitis or ILD in 6 of 131 (4.6%)[5] and in 10 of 287 (3.5%) patients, respectively.[6]