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 OP

OP is characterized by radiological features of bilateral alveolar consolidations, GGOs, and patchy infiltrates with air bronchograms. The lack of any infectious pathogens in BAL samples and a CD8+ lymphocytic alveolitis is suggestive of a lung immunoreactive process. There is rapid resolution with corticosteroids, but relapse after treatment interruption. Such recurrence could be the consequence of the long mean elimination half-life of Nivolumab, approximately 27 days, and thus needing >4 months for complete tissue clearance.[23] All of these findings are well-known characteristics of bronchiolitis with OP and generally considered as a good surrogate marker supporting the immune origin, avoiding open-lung biopsy.[23] Three cases of OP related to nivolumab[23–25] have been described in the literature.

Sano et al[24] described a case of a 70-year-old woman with vaginal melanoma with multiple metastases in her brain, lung, liver, pancreas, pelvis, and bone. She was treated with nivolumab 2 mg/kg every 3 weeks. Although she was asymptomatic, crackles were auscultated on physical examination and CT scan findings of GGOs and consolidation with air bronchograms were noted.[24] The patient had a bronchoscopy with BAL and lung biopsy. She was started on steroids, with a prolonged taper after stopping nivolumab.[24]

Nakashima et al[25] reported a 70-year-old woman never smoker who had MM with pulmonary metastasis. She was taking nivolumab 2 mg/kg every 3 weeks and presented with fever, anorexia, exertional dyspnea and productive cough. Negative BAL and lung biopsy studies were obtained. She was started on steroids, with relief of her symptoms.

A 70-year-old man with sarcomatoid carcinoma and metastasis to the small intestine and spleen was noted by Gounant et al.[23] He was treated with nivolumab 3 mg/kg every 2 weeks. He presented with fever, exertional dyspnea, and productive cough. The physical examination revealed crackles. He was started on steroids, with improvement of his symptoms.