TY - JOUR
T1 - Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy
AU - Naidoo, Jarushka
AU - Wang, Xuan
AU - Woo, Kaitlin M.
AU - Iyriboz, Tunc
AU - Halpenny, Darragh
AU - Cunningham, Jane
AU - Chaft, Jamie E.
AU - Segal, Neil H.
AU - Callahan, Margaret K.
AU - Lesokhin, Alexander M.
AU - Rosenberg, Jonathan
AU - Voss, Martin H.
AU - Rudin, Charles M.
AU - Rizvi, Hira
AU - Hou, Xue
AU - Rodriguez, Katherine
AU - Albano, Melanie
AU - Gordon, Ruth Ann
AU - Leduc, Charles
AU - Rekhtman, Natasha
AU - Harris, Bianca
AU - Menzies, Alexander M.
AU - Guminski, Alexander D.
AU - Carlino, Matteo S.
AU - Kong, Benjamin Y.
AU - Wolchok, Jedd D.
AU - Postow, Michael A.
AU - Long, Georgina V.
AU - Hellmann, Matthew D.
N1 - Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.68.2005
DO - 10.1200/JCO.2016.68.2005
M3 - Article
C2 - 27646942
AN - SCOPUS:85014010627
SN - 0732-183X
VL - 35
SP - 709
EP - 717
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -