Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy Journal Article


Authors: Naidoo, J.; Wang, X.; Woo, K. M.; Iyriboz, T.; Halpenny, D.; Cunningham, J.; Chaft, J. E.; Segal, N. H.; Callahan, M. K.; Lesokhin, A. M.; Rosenberg, J.; Voss, M. H.; Rudin, C. M.; Rizvi, H.; Hou, X.; Rodriguez, K.; Albano, M.; Gordon, R. A.; Leduc, C.; Rekhtman, N.; Harris, B.; Menzies, A. M.; Guminski, A. D.; Carlino, M. S.; Kong, B. Y.; Wolchok, J. D.; Postow, M. A.; Long, G. V.; Hellmann, M. D.
Article Title: Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy
Abstract: Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/ programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlyingmalignancywere examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patientswho received anti-PD-1/PD-L1mAbs, pneumonitis developed in 43 (5%; 95%CI, 3%to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from9 days to 19.2months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P , .01). Incidencewas similar in patientswithmelanoma and non-small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [P = 1.0]; combination, 11 of 115 v four of 57 [P = .78]). Seventy-two percent (31 of 43) of caseswere grade 1 to 2, and 86%(37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of deathwas pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion Pneumonitis associated with anti-PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti-PD-1/PD-L1 mAbs are combined with anti-cytotoxic T-cell lymphocyte-4 mAb. Most events are low grade and improve/ resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 35
Issue: 7
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2017-03-01
Start Page: 709
End Page: 717
Language: English
DOI: 10.1200/jco.2016.68.2005
PROVIDER: scopus
PUBMED: 27646942
PMCID: PMC5559901
DOI/URL:
Notes: Article -- Export Date: 3 April 2017 -- Source: Scopus
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MSK Authors
  1. Tunc Iyriboz
    10 Iyriboz
  2. Natasha Rekhtman
    279 Rekhtman
  3. Jedd D Wolchok
    756 Wolchok
  4. Neil Howard Segal
    139 Segal
  5. Michael Andrew Postow
    230 Postow
  6. Martin Henner Voss
    169 Voss
  7. Jamie Erin Chaft
    163 Chaft
  8. Margaret Kathleen Callahan
    135 Callahan
  9. Ruth-Ann Roman
    33 Roman
  10. Alexander Meyer Lesokhin
    135 Lesokhin
  11. Matthew David Hellmann
    257 Hellmann
  12. Jonathan Eric Rosenberg
    308 Rosenberg
  13. Charles Rudin
    231 Rudin
  14. Jarushka Naidoo
    32 Naidoo
  15. Kaitlin Marie Woo
    100 Woo
  16. Charles   Leduc
    13 Leduc
  17. Bianca   Harris
    6 Harris
  18. Hira Abbas Rizvi
    45 Rizvi
  19. Xue Hou
    1 Hou