Medline ® Abstracts for References 58,59
of 'Toxicities associated with checkpoint inhibitor immunotherapy'
PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course.
Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, Hatabu H, Ott PA, Armand PF, Hodi FS
Clin Cancer Res. 2016;22(24):6051. Epub 2016 Aug 17.
PURPOSE: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.
EXPERIMENTAL DESIGN: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.
RESULTS: Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.
CONCLUSIONS: PD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051-60.©2016 AACRSee related commentary by Castanon, p. 5956.
Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. Mizuki_Nishino@dfci.harvard.edu.
Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy.
Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, Rosenberg J, Voss MH, Rudin CM, Rizvi H, Hou X, Rodriguez K, Albano M, Gordon RA, Leduc C, Rekhtman N, Harris B, Menzies AM, Guminski AD, Carlino MS, Kong BY, Wolchok JD, Postow MA, Long GV, Hellmann MD
J Clin Oncol. 2017;35(7):709. Epub 2016 Sep 30.
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-4 mAb 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 underlying malignancy were examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patients who received anti-PD-1/PD-L1 mAbs, 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 from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%]v 24 of 716 [3%]; P<.01). Incidence was similar in patients with melanoma 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 cases were 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 death was 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 withdrug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.
Jarushka Naidoo, Kaitlin M. Woo, Tunc Iyriboz, Darragh Halpenny, Jane Cunningham, Jamie E. Chaft, Neil H. Segal, Margaret K. Callahan, Alexander M. Lesokhin, Jonathan Rosenberg, Martin H. Voss, Charles M. Rudin, Hira Rizvi, Xue Hou, Katherine Rodriguez, Melanie Albano, Ruth-Ann Gordon, Charles Leduc, Natasha Rekhtman, Bianca Harris, Jedd D. Wolchok, Michael A. Postow, and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft, Neil H. Segal, Margaret K. Callahan, Alexander M. Lesokhin, Jonathan Rosenberg, Martin H. Voss, Charles M. Rudin, Jedd D. Wolchok, Michael A. Postow, and Matthew D. Hellmann, Weill Cornell Medical College, New York, NY; Jarushka Naidoo, Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore, MD; Xuan Wang, Peking University Cancer Hospital and Institute, Beijing; Xue Hou, Sun Yat-sen University Cancer Center, Guangdong Province, People's Republic of China; Xuan Wang, Matteo S. Carlino, Benjamin Y. Kong, and Georgina V. Long, The U