PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course

被引:394
作者
Nishino, Mizuki [1 ,2 ]
Ramaiya, Nikhil H. [1 ,2 ]
Awad, Mark M. [3 ]
Sholl, Lynette M. [4 ]
Maattala, Jennifer A. [3 ]
Taibi, Myriam [3 ]
Hatabu, Hiroto [1 ,2 ]
Ott, Patrick A. [3 ]
Armand, Philippe F. [3 ]
Hodi, F. Stephen [3 ]
机构
[1] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA
关键词
CELL LUNG-CANCER; DRUG-RELATED PNEUMONITIS; LONG-TERM SAFETY; ADVANCED MELANOMA; RECEIVING NIVOLUMAB; UNTREATED MELANOMA; MAMMALIAN TARGET; ADVERSE EVENTS; IPILIMUMAB; PEMBROLIZUMAB;
D O I
10.1158/1078-0432.CCR-16-1320
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C)2016 AACR.
引用
收藏
页码:6051 / 6060
页数:10
相关论文
共 30 条
[1]   PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma [J].
Ansell, Stephen M. ;
Lesokhin, Alexander M. ;
Borrello, Ivan ;
Halwani, Ahmad ;
Scott, Emma C. ;
Gutierrez, Martin ;
Schuster, Stephen J. ;
Millenson, Michael M. ;
Cattry, Deepika ;
Freeman, Gordon J. ;
Rodig, Scott J. ;
Chapuy, Bjoern ;
Ligon, Azra H. ;
Zhu, Lili ;
Grosso, Joseph F. ;
Kim, Su Young ;
Timmerman, John M. ;
Shipp, Margaret A. ;
Armand, Philippe .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :311-319
[2]   Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].
Borghaei, H. ;
Paz-Ares, L. ;
Horn, L. ;
Spigel, D. R. ;
Steins, M. ;
Ready, N. E. ;
Chow, L. Q. ;
Vokes, E. E. ;
Felip, E. ;
Holgado, E. ;
Barlesi, F. ;
Kohlhaeufl, M. ;
Arrieta, O. ;
Burgio, M. A. ;
Fayette, J. ;
Lena, H. ;
Poddubskaya, E. ;
Gerber, D. E. ;
Gettinger, S. N. ;
Rudin, C. M. ;
Rizvi, N. ;
Crino, L. ;
Blumenschein, G. R. ;
Antonia, S. J. ;
Dorange, C. ;
Harbison, C. T. ;
Finckenstein, F. Graf ;
Brahmer, J. R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639
[3]   Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].
Brahmer, Julie ;
Reckamp, Karen L. ;
Baas, Paul ;
Crino, Lucio ;
Eberhardt, Wilfried E. E. ;
Poddubskaya, Elena ;
Antonia, Scott ;
Pluzanski, Adam ;
Vokes, Everett E. ;
Holgado, Esther ;
Waterhouse, David ;
Ready, Neal ;
Gainor, Justin ;
Aren Frontera, Osvaldo ;
Havel, Libor ;
Steins, Martin ;
Garassino, Marina C. ;
Aerts, Joachim G. ;
Domine, Manuel ;
Paz-Ares, Luis ;
Reck, Martin ;
Baudelet, Christine ;
Harbison, Christopher T. ;
Lestini, Brian ;
Spigel, David R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135
[4]   Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates [J].
Brahmer, Julie R. ;
Drake, Charles G. ;
Wollner, Ira ;
Powderly, John D. ;
Picus, Joel ;
Sharfman, William H. ;
Stankevich, Elizabeth ;
Pons, Alice ;
Salay, Theresa M. ;
McMiller, Tracee L. ;
Gilson, Marta M. ;
Wang, Changyu ;
Selby, Mark ;
Taube, Janis M. ;
Anders, Robert ;
Chen, Lieping ;
Korman, Alan J. ;
Pardoll, Drew M. ;
Lowy, Israel ;
Topalian, Suzanne L. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (19) :3167-3175
[5]   Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer [J].
Garon, Edward B. ;
Rizvi, Naiyer A. ;
Hui, Rina ;
Leighl, Natasha ;
Balmanoukian, Ani S. ;
Eder, Joseph Paul ;
Patnaik, Amita ;
Aggarwal, Charu ;
Gubens, Matthew ;
Horn, Leora ;
Carcereny, Enric ;
Ahn, Myung-Ju ;
Felip, Enriqueta ;
Lee, Jong-Seok ;
Hellmann, Matthew D. ;
Hamid, Omid ;
Goldman, Jonathan W. ;
Soria, Jean-Charles ;
Dolled-Filhart, Marisa ;
Rutledge, Ruth Z. ;
Zhang, Jin ;
Lunceford, Jared K. ;
Rangwala, Reshma ;
Lubiniecki, Gregory M. ;
Roach, Charlotte ;
Emancipator, Kenneth ;
Gandhi, Leena .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2018-2028
[6]   Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer [J].
Gettinger, Scott N. ;
Horn, Leora ;
Gandhi, Leena ;
Spigel, David R. ;
Antonia, Scott J. ;
Rizvi, Naiyer A. ;
Powderly, John D. ;
Heist, Rebecca S. ;
Carvajal, Richard D. ;
Jackman, David M. ;
Sequist, Lecia V. ;
Smith, David C. ;
Leming, Philip ;
Carbone, David P. ;
Pinder-Schenck, Mary C. ;
Topalian, Suzanne L. ;
Hodi, F. Stephen ;
Sosman, Jeffrey A. ;
Sznol, Mario ;
McDermott, David F. ;
Pardoll, Drew M. ;
Sankar, Vindira ;
Ahlers, Christoph M. ;
Salvati, Mark ;
Wigginton, Jon M. ;
Hellmann, Matthew D. ;
Kollia, Georgia D. ;
Gupta, Ashok K. ;
Brahmer, Julie R. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (18) :2004-U32
[7]   Safety and Tumor Responses with Lambrolizumab (Anti-PD-1) in Melanoma [J].
Hamid, Omid ;
Robert, Caroline ;
Daud, Adil ;
Hodi, F. Stephen ;
Hwu, Wen-Jen ;
Kefford, Richard ;
Wolchok, Jedd D. ;
Hersey, Peter ;
Joseph, Richard W. ;
Weber, Jeffrey S. ;
Dronca, Roxana ;
Gangadhar, Tara C. ;
Patnaik, Amita ;
Zarour, Hassane ;
Joshua, Anthony M. ;
Gergich, Kevin ;
Elassaiss-Schaap, Jeroen ;
Algazi, Alain ;
Mateus, Christine ;
Boasberg, Peter ;
Tumeh, Paul C. ;
Chmielowski, Bartosz ;
Ebbinghaus, Scot W. ;
Li, Xiaoyun Nicole ;
Kang, S. Peter ;
Ribas, Antoni .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (02) :134-144
[8]   Improved Survival with Ipilimumab in Patients with Metastatic Melanoma [J].
Hodi, F. Stephen ;
O'Day, Steven J. ;
McDermott, David F. ;
Weber, Robert W. ;
Sosman, Jeffrey A. ;
Haanen, John B. ;
Gonzalez, Rene ;
Robert, Caroline ;
Schadendorf, Dirk ;
Hassel, Jessica C. ;
Akerley, Wallace ;
van den Eertwegh, Alfons J. M. ;
Lutzky, Jose ;
Lorigan, Paul ;
Vaubel, Julia M. ;
Linette, Gerald P. ;
Hogg, David ;
Ottensmeier, Christian H. ;
Lebbe, Celeste ;
Peschel, Christian ;
Quirt, Ian ;
Clark, Joseph I. ;
Wolchok, Jedd D. ;
Weber, Jeffrey S. ;
Tian, Jason ;
Yellin, Michael J. ;
Nichol, Geoffrey M. ;
Hoos, Axel ;
Urba, Walter J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (08) :711-723
[9]  
Larkin J, 2015, NEW ENGL J MED, V373, P23, DOI [10.1056/NEJMoa1504030, 10.1056/NEJMc1509660]
[10]   Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab [J].
McDermott, David F. ;
Drake, Charles G. ;
Sznol, Mario ;
Choueiri, Toni K. ;
Powderly, John D. ;
Smith, David C. ;
Brahmer, Julie R. ;
Carvajal, Richard D. ;
Hammers, Hans J. ;
Puzanov, Igor ;
Hodi, F. Stephen ;
Kluger, Harriet M. ;
Topalian, Suzanne L. ;
Pardoll, Drew M. ;
Wigginton, Jon M. ;
Kollia, Georgia D. ;
Gupta, Ashok ;
McDonald, Dan ;
Sankar, Vindira ;
Sosman, Jeffrey A. ;
Atkins, Michael B. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (18) :2013-U42