Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2018

Open Access 01-12-2018 | Case report

High incidence and early onset of nivolumab-induced pneumonitis: four case reports and literature review

Authors: N. Koyama, O. Iwase, E. Nakashima, K. Kishida, T. Kondo, Y. Watanabe, H. Takahashi, Y. Umebayashi, Y. Ogawa, H. Miura

Published in: BMC Pulmonary Medicine | Issue 1/2018

Login to get access

Abstract

Background

Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis.

Case presentation

We present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis. In our series, 20% of patients who were treated with nivolumab developed pneumonitis, all of which occurred approximately 2 weeks after the initiation of nivolumab treatment. Prompt recognition of the nivolumab-induced pneumonitis allowed for successful resolution. Computed tomography scan images of the patients demonstrated predominantly cryptogenic organizing pneumonia patterns. All patients were males, who had been heavily treated with antitumor drugs prior to nivolumab.

Conclusions

Our case series showed that nivolumab had a high incidence of drug-induced pneumonitis with early onset, supporting the need for renewed attention to nivolumab-induced pneumonitis, particularly in patients with a history of heavy antitumor treatments.
Literature
1.
go back to reference Wang C, Thudium KB, Han M, Wang XT, Huang H, Feingersh D, Garcia C, Wu Y, Kuhne M, Srinivasan M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2(9):846–56.CrossRefPubMed Wang C, Thudium KB, Han M, Wang XT, Huang H, Feingersh D, Garcia C, Wu Y, Kuhne M, Srinivasan M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2(9):846–56.CrossRefPubMed
2.
go back to reference Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.CrossRefPubMedPubMedCentral Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.CrossRefPubMedPubMedCentral
3.
go back to reference Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.CrossRefPubMedPubMedCentral Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.CrossRefPubMedPubMedCentral
4.
go back to reference Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.CrossRefPubMedPubMedCentral Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.CrossRefPubMedPubMedCentral
5.
go back to reference Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.CrossRefPubMedPubMedCentral Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.CrossRefPubMedPubMedCentral
6.
go back to reference Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9.CrossRefPubMed Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9.CrossRefPubMed
7.
go back to reference Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent Squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.CrossRefPubMedPubMedCentral Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent Squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.CrossRefPubMedPubMedCentral
8.
go back to reference Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncol. 2016;2(12):1607-16. Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncol. 2016;2(12):1607-16.
9.
go back to reference Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, Hatabu H, Ott PA, Armand P, Hodi FS. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051-60. Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, Hatabu H, Ott PA, Armand P, Hodi FS. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051-60.
10.
go back to reference Freeman-Keller M, Kim Y, Cronin H, Richards A, Gibney G, Weber JS. Nivolumab in Resected and Unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res. 2016;22(4):886–94.CrossRefPubMed Freeman-Keller M, Kim Y, Cronin H, Richards A, Gibney G, Weber JS. Nivolumab in Resected and Unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res. 2016;22(4):886–94.CrossRefPubMed
11.
go back to reference Kato T, Masuda N, Nakanishi Y, Takahashi M, Hida T, Sakai H, Atagi S, Fujita S, Tanaka H, Takeda K, et al. Nivolumab-induced interstitial lung disease analysis of two phase II studies patients with recurrent or advanced non-small-cell lung cancer. Lung Cancer. 2017;104:111–8.CrossRefPubMed Kato T, Masuda N, Nakanishi Y, Takahashi M, Hida T, Sakai H, Atagi S, Fujita S, Tanaka H, Takeda K, et al. Nivolumab-induced interstitial lung disease analysis of two phase II studies patients with recurrent or advanced non-small-cell lung cancer. Lung Cancer. 2017;104:111–8.CrossRefPubMed
12.
go back to reference Kudoh S, Kato H, Nishiwaki Y, Fukuoka M, Nakata K, Ichinose Y, Tsuboi M, Yokota S, Nakagawa K, Suga M, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med. 2008;177(12):1348–57.CrossRefPubMed Kudoh S, Kato H, Nishiwaki Y, Fukuoka M, Nakata K, Ichinose Y, Tsuboi M, Yokota S, Nakagawa K, Suga M, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med. 2008;177(12):1348–57.CrossRefPubMed
13.
go back to reference Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709–17.CrossRefPubMed Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709–17.CrossRefPubMed
15.
go back to reference Belloli EA, Beckford R, Hadley R, Flaherty KR. Idiopathic non-specific interstitial pneumonia. Respirology. 2016;21(2):259–68.CrossRefPubMed Belloli EA, Beckford R, Hadley R, Flaherty KR. Idiopathic non-specific interstitial pneumonia. Respirology. 2016;21(2):259–68.CrossRefPubMed
16.
go back to reference Koelzer VH, Rothschild SI, Zihler D, Wicki A, Willi B, Willi N, Voegeli M, Cathomas G, Zippelius A, Mertz KD. Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors-an autopsy study. J Immunother Cancer. 2016;4:13.CrossRefPubMedPubMedCentral Koelzer VH, Rothschild SI, Zihler D, Wicki A, Willi B, Willi N, Voegeli M, Cathomas G, Zippelius A, Mertz KD. Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors-an autopsy study. J Immunother Cancer. 2016;4:13.CrossRefPubMedPubMedCentral
Metadata
Title
High incidence and early onset of nivolumab-induced pneumonitis: four case reports and literature review
Authors
N. Koyama
O. Iwase
E. Nakashima
K. Kishida
T. Kondo
Y. Watanabe
H. Takahashi
Y. Umebayashi
Y. Ogawa
H. Miura
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2018
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-018-0592-x

Other articles of this Issue 1/2018

BMC Pulmonary Medicine 1/2018 Go to the issue