Cancer Immunology Miniatures

Anti–PD-1 Inhibitor–Related Pneumonitis inNon–Small Cell Lung CancerMizuki Nishino1, Emily S. Chambers2, Curtis R. Chong2, Nikhil H. Ramaiya1, StacyW. Gray2,J. Paul Marcoux2, Hiroto Hatabu1, Pasi A. J€anne2, F. Stephen Hodi2, and Mark M. Awad2

Abstract

The recent approval of two PD-1 inhibitors for the treatment ofnon–small cell lung cancer (NSCLC) has rapidly led to thewidespreaduseof these agents in oncologypractices. Pneumonitishas been recognized as a potentially life-threatening adverse eventamongNSCLCpatients treatedwithPD-1 inhibitors; however, thedetailed clinical and radiographic manifestations of this entityremain to be described. We report on two cases of anti–PD-1pneumonitis in advanced NSCLC patients treated with nivolu-mab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheraldistribution on CT, demonstrating a radiographic pattern ofcryptogenic organizing pneumonia. Consolidations were exten-

sive and rapidly developed within 8 weeks of therapy in bothcases. Both patients were treated with corticosteroids with subse-quent improvement of respiratory symptoms and radiographicfindings. One patient experienced recurrent pneumonitis aftercompleting corticosteroid taper, or a "pneumonitis flare," in theabsence of nivolumab retreatment, with subsequent improve-ment upon corticosteroid readministration. With the increasinguse of immune checkpoint inhibitors in a growing number oftumor types, awareness of the radiographic and clinical manifes-tations of PD-1 inhibitor–related pneumonitis will be critical forthe prompt diagnosis andmanagement of this potentially seriousadverse event. Cancer Immunol Res; 4(4); 289–93. �2016 AACR.

IntroductionImmune checkpoint blockade with PD-1 inhibitors has revo-

lutionized the treatment of an increasing number of tumor types,including melanoma and non–small cell lung cancer (NSCLC;refs. 1–7). Nivolumab has demonstrated a survival benefit overdocetaxel in both squamous (8) and nonsquamous (9) NSCLCs,and was granted FDA approval for squamous NSCLC in March2015 and for nonsquamous NSCLC in October 2015. AnotherPD-1 inhibitor, pembrolizumab, has also shown marked antitu-mor activity in previously treated NSCLC (10) and was grantedaccelerated FDA approval for PD-L1þ NSCLCs in October 2015.

With more widespread prescribing of PD-1 inhibitors, promptrecognition of serious toxicities is necessary for the safe use ofthese agents. Among immune-related adverse events (irAE) notedduring trials of PD-1 inhibitors, pneumonitis has been recognizedas an "event of special interest," occurring at a rate of 3% (9/296)and resulting in three treatment-related deaths (2 patients withNSCLC and 1 patient with colorectal cancer) in a phase I trial ofnivolumab (5). The long-term safety in the NSCLC cohort fromthis phase I trial was updated, and pneumonitis was reported in7% (9/129), with three pneumonitis-associated deaths (1). In aphase II trial of nivolumab in squamous NSCLC, pneumonitis

was one of the most common irAEs, occurring in 5% of patients(6/117), including 4 patients with grade 3 pneumonitis (3).

In response to the increasing awareness of pneumonitis as aserious irAE, our group has described clinical and radiographicfeatures of anti–PD-1 pneumonitis in melanoma patients treatedin trials of nivolumab (11). However, this entity has not beenpreviously reported specifically in the NSCLC population. Giventhe large number of advanced lung cancer patients diagnosed inthe United States every year who could potentially be treated withimmune checkpoint blockade, and the fact that many symptomsof PD-1 inhibitor–related pneumonitis overlap with commonsymptoms of lung cancer, clinical and radiographic descriptionsof this potentially life-threatening, but treatable, entity are urgent-ly needed.

We report on two cases of anti–PD-1 pneumonitis in advancedNSCLC patients treated with nivolumab after its FDA approval.Improving our understanding of PD-1 inhibitor–related pneu-monitis will enable radiologists and oncologists to accuratelyrecognize this entity andpromptly provide appropriate treatment.

Materials and MethodsAmong the advanced NSCLC patients treated with nivolumab

after its FDA approval as a part of clinical care at our institution,two cases of anti–PD-1–related pneumonitis were identifiedbased on the review of the medical records. The imaging studiesof these patients were retrospectively reviewed with an Institu-tional Review Board–approved clinical research protocol. ChestCT scans at baseline, during therapy, and at follow-up werereviewed by a consensus of three radiologists with expertise inthoracic and oncologic imaging (M. Nishino, N.H. Ramaiya, andH.Hatabu) for findings of pneumonitis, as described (11, 12). CTfindings of pneumonitis were assessed for (i) extent in upper,middle, and lower lungs (none, <5%, 5%–25%, 25%–50%,

1Department of Radiology, Brigham andWomen's Hospital andDana-Farber Cancer Institute, Boston, Massachusetts. 2Department of Med-ical Oncology and Department of Medicine, Dana-Farber CancerInstitute and Brigham andWomen's Hospital, Boston, Massachusetts.

Corresponding Author: Mizuki Nishino, Brigham and Women's Hospital andDana-Farber Cancer Institute, 450 Brookline Avenue, Boston MA, 02215. Phone:617-582-7163; Fax: 617-582-8574; E-mail: Mizuki_Nishino@dfci.harvard.edu

doi: 10.1158/2326-6066.CIR-15-0267

�2016 American Association for Cancer Research.

CancerImmunologyResearch

www.aacrjournals.org 289

on April 9, 2021. © 2016 American Association for Cancer Research. cancerimmunolres.aacrjournals.org Downloaded from

Published OnlineFirst February 10, 2016; DOI: 10.1158/2326-6066.CIR-15-0267

>50%); (ii) distributions in terms of (a) peripheral, diffuse,central, or mixed and (b) upper, lower, diffuse, multifocal, orfocal; (iii) lobar involvement; and (iv) specific CT findings,including traction bronchiectasis, consolidation, reticular opaci-ties, ground-glass opacities (GGO), centrilobular nodularity, andhoneycombing. In each case, radiographic patterns of pneumo-nitis were classified according to American Thoracic Society/European Respiratory Society international multidisciplinaryclassification of interstitial pneumonias and the related condi-tions as (i) usual interstitial pneumonia pattern; (ii) nonspecificinterstitial pneumonia (NSIP) pattern; (iii) cryptogenic organiz-ing pneumonia (COP) pattern; (iv) acute interstitial pneumonia(AIP)/acute respiratory distress syndrome (ARDS) pattern; (v)hypersensitivity pneumonitis pattern; and (vi) not applicable, asdescribed (11–13). Clinical presentation and treatment course ofpneumonitis were obtained from the medical record review.

Case ReportsCase 1 is a 72-year-old man with stage IV squamous NSCLC

who had disease progression after four cycles of carboplatin andpaclitaxel. The patient was then treated with second-line nivolu-mab monotherapy at a standard dose of 3 mg/kg every 2 weeks.After four doses of nivolumab, the patient reported only mildfatigue but no respiratory symptoms. Chest CT scan at 8 weeks oftherapy demonstrated new GGOs, reticular opacities, and con-solidation in lower lobes, with a peripheral and lower distribu-tion, representing a COP pattern based on the radiographicappearance (Fig. 1A and B). On the same CT, the dominant rightupper lobe tumor had markedly decreased in size compared withbaseline, indicating response to therapy.

Over the subsequent weeks while on continued nivolumabtherapy, the patient developed progressive dyspnea with coughand wheezing, but no fever. A follow-up chest CT at 15 weeks oftherapy showed a significant increase in the radiographic findingswhich involved all lung lobes (Fig. 1C and D). The distribution ofthe findings was peripheral and multifocal, representing a COPpattern, and the progressive nature was also indicative of ARDS.Nivolumab was held, and the patient was treated with 60 mg ofprednisone by mouth daily as an outpatient, with rapid clinicalimprovement. He was also placed on trimethoprim-sulfamethox-azole for pneumocystis prophylaxis. Four weeks later, while thepatientwas onprednisone taper, a repeat scanof the chest showed amarked decrease of consolidations (Fig. 1E and F), and residualGGOs showeda "reversedhalo" sign,withcentralGGOsurroundedby dense consolidation of crescentic shape (Fig. 1F; ref. 14). Thepatient had been on a corticosteroid taper for a total of 8 weeksbefore prednisonewasdiscontinuedaltogether,withnear-completeresolution of his pneumonitis-related symptoms at that time.

However, within 4 weeks after discontinuation of prednisone,without restarting nivolumab or initiation of any other systemiccancer therapy, the patient again developed respiratory symp-toms, including dyspnea, cough, and wheezing, but no fever.Chest CT scan showed bilateral dense consolidations with GGOsand reticular opacities in peripheral and multifocal distributions,again representing a COP pattern (Fig. 1G and H) as noted at theonset of PD-1 pneumonitis. Given the similarities in clinical andradiographic manifestations with the first episode, the findingswere most indicative of recurrent pneumonitis after discontinu-ation of prednisone, or a "pneumonitis flare" in the absence ofnivolumab retreatment. The patient restarted prednisone at a dose

of 60 mg daily with levofloxacin at a dose of 750 mg by mouthdaily, again with improvement in cough, wheezing, and dyspnea.A follow-up CT at 2 weeks on the second course of prednisonetreatment showed resolving consolidations and GGOs (Fig. 1Iand J).

Case 2 is an 83-year-old woman who originally had a stage IIANSCLCwith neuroendocrine features. She underwent right upperlobectomy and had declined adjuvant chemotherapy. She wassubsequently found to have liver metastases and was felt to be apoor candidate for cytotoxic chemotherapy. She was treated withnivolumab, and after 4weeks of therapy, the patient was admittedto the hospital with an increasing dry cough, dyspnea, andhypoxemia. A CT scan on admission showed new multifocalareas of GGO, reticular opacities, and consolidation in the leftlung with a peripheral distribution (Fig. 2A–D), demonstrating aCOP pattern based on the radiographic appearance. The livermetastasis decreased in size, in response to nivolumab. She wastreated with a prednisone taper, starting at a dose of 60 mg daily,along with sulfamethoxazole-trimethoprim. A chest CT scantaken 2 weeks later showed marked decrease of the multifocallung opacities. The patient has completed a prednisone taper overthe past several weeks. Due to the severity of this patient'spneumonitis, nivolumab was not restarted and she was startedon another systemic therapy.

DiscussionThe present report provides the first detailed description of the

clinical and radiographic characteristics of PD-1 inhibitor–relatedpneumonitis in NSCLC patients treated with nivolumab, whichwas administered as part of standard clinical care and not in thetrial setting. The onset of pneumonitis in both cases was ratherearly, developing within 8 weeks after treatment initiation. Bothpatients were symptomatic with cough and shortness of breath,and 1 patient experienced hypoxemia. Imaging findings weresimilar in the two cases, with GGOs and consolidations in aperipheral distribution, which is radiographically indicative of aCOP pattern based on the radiographic appearance on CT. Bothcases were successfully treated with oral corticosteroids, withmarked improvement of clinical symptoms and radiographicfindings; however, 1 patient experienced a "pneumonitis flare"after completing a prednisone taper, which was responsive toreinitiation of corticosteroids.

Multifocal consolidationswere themajor radiographicfindingsof pneumonitis in the two cases; the consolidations on CT wereextensive anddeveloped rapidlywithin 2months, whichmaybe anotable feature of the entity. Because of this feature, CT scans ofboth cases at the onset of pneumonitis were initially interpreted as"infectious pneumonia versus tumor progression." Althoughthese differential diagnoses are reasonable, treatment-relatedpneumonitis should also be strongly considered in patientsreceiving PD-1 inhibitors presenting with new pulmonary find-ings on imaging (11). The respiratory symptoms of pneumonitis,including cough, shortness of breath, and hypoxemia, overlapwith the symptoms of advanced lung cancer itself, providingadditional challenges for early identification of anti–PD-1 pneu-monitis specifically among NSCLC patients. The increased aware-ness of the entity among cancer care providers and the multidis-ciplinary approach, including oncologists, radiologists, and pul-monologists, are necessary for prompt diagnosis and manage-ment of this potentially serious adverse event.

Nishino et al.

Cancer Immunol Res; 4(4) April 2016 Cancer Immunology Research290

on April 9, 2021. © 2016 American Association for Cancer Research. cancerimmunolres.aacrjournals.org Downloaded from

Published OnlineFirst February 10, 2016; DOI: 10.1158/2326-6066.CIR-15-0267

A, B. At 8 weeks of nivolumab therapy

Niv

olum

abP

redn

ison

eP

redn

ison

eC, D. At 15 weeks of nivolumab therapy

E, F. 4 weeks after starting prednisone

G, H. 4 weeks after completion of prednisone tapering

I, J. 2 weeks after restarting prednisoneI J

G H

E F

C D

A B

Figure 1.Chest CT images for case 1. A and B,chest CT at 8 weeks of nivolumabtherapy demonstrated new GGO,reticular opacities, and consolidation inlower lobes predominantly on the left,with a peripheral and lower distribution,radiographically representing a COPpattern (arrows). C and D, on chest CT at15 weeks of therapy, the findingssignificantly increased and involved alllobes, with multifocal areas of GGO,reticular opacities, and consolidation(arrows), as well as centrilobularnodularity and traction bronchiectasis inpredominantly peripheral distribution.The overall features demonstrated aCOP pattern, while the progressivenature was also indicative of developingARDS. E and F, further follow-upCT after4 weeks of prednisone treatmentshowed a significant decrease of the CTfindings with residual GGOs,demonstrating a "reversed halo" signwith central GGO surrounded by denseair-space consolidation of crescenticshape (F, arrows), which has beenreported as a radiographicmanifestation of COP. G and H, chest CTscan 4 weeks after the completion ofprednisone treatment showeddevelopment of dense consolidationswith GGOs and reticular opacities(arrows) in peripheral and multifocaldistributions, involving both upper andlower lobes, again demonstrating COPpattern as noted during the first episodeof PD-1 pneumonitis. Given the similarityof radiographic and clinicalmanifestationswith the first episode, thepatient restarted prednisone fortreatment of a "pneumonitis flare." I andJ, follow-up chest CT taken 2weeks afterstarting the second course ofprednisone therapy demonstrateddecrease of consolidation and GGOs(arrows), indicating improvingpneumonitis in response tocorticosteroid therapy.

Anti–PD-1 Inhibitor–Related Pneumonitis in Lung Cancer

www.aacrjournals.org Cancer Immunol Res; 4(4) April 2016 291

on April 9, 2021. © 2016 American Association for Cancer Research. cancerimmunolres.aacrjournals.org Downloaded from

Published OnlineFirst February 10, 2016; DOI: 10.1158/2326-6066.CIR-15-0267

There has been one previously published report of the radio-graphic appearance of anti–PD-1 pneumonitis, which included 3melanoma patients (11). The report included a spectrum ofradiographic and clinical manifestations, with 2 patients showingan AIP/ARDS pattern requiring admission to intensive care units,and 1 patient with a NSIP pattern who was treated with oralcorticosteroids as an outpatient andwas able to restart nivolumabtherapy. Although similarities and differences of the radiographicand clinical features of anti–PD-1 pneumonitis across differenttumor types need to be further studied in larger cohorts, thepresent report describes a COP pattern consistently noted in bothpatients, indicating it may be one of the leading radiographicpatterns of this entity among the NSCLC population, which wasnot described in the previous report of melanoma patients.

Both patients were successfully treated by oral prednisone taperwith clinical and radiographic improvement. However, the patientdescribed in case 1 experienced recurrent pneumonitis after dis-continuation of prednisone, with a very similar radiographic COPpattern as seen in the first episode, indicating a "pneumonitisflare"after completing a steroid taper. Notably, a pneumonitis flareoccurred without restarting nivolumab, which may be a uniquefeature of immune-related pneumonitis. Although the detailedmechanisms of this unusual phenomenon remain to be investi-gated, it may be at least in part related to the durable nature of theeffect of immune checkpoint inhibitors that have been shown tobeassociated with durable and persistent response after drug discon-tinuation (6). This observation, although limited to one case in ourinitial experience, raises an important question as to when todiscontinue corticosteroids in those who have experienced PD-1pneumonitis. It may also indicate the needs for additional cautionwhen discussing nivolumab retreatment in these patients.

Prolonged use of corticosteroids raises a concern for a possiblenegative impact on the antitumor efficacy of immune checkpointinhibitors. In a recent retrospective review of 298 melanomapatients treated with ipilimumab, 254 (85%) experienced an irAEof any grade, and 103 patients (35%) required systemic corticos-teroids to treat an irAE; however, overall survival and time totreatment failurewere not affected by the occurrence of irAEs or bythe need for systemic corticosteroids (15). Additional studies willbe needed to determine if these findings will also extend topatients requiring corticosteroids for the treatment of irAEs afterPD-1 inhibitor administration.

Neither patient underwent bronchoscopy or biopsy for pneu-monitis. The precise role of bronchoscopy and bronchoalveolarlavage (BAL) in themanagement of PD-1 pneumonitis is currentlyunclear, but BAL may help identify an underlying pulmonaryinfection. Without biopsy, both patients in the present series lackhistologic assessments of pneumonitis, which is often the casewith patients who have known advanced malignancy receivingsystemic therapy (12, 16). A COP pattern of pneumonitis in thepresent cases was characterized by the radiographic appearance ofthe lung abnormalities of pneumonitis, based on the assessmentof extent, distribution, and specific CT findings, as describedpreviously (11, 12).

In conclusion, in our initial experience with anti–PD-1–related pneumonitis in NSCLC, both cases showed a radio-graphic COP pattern with extensive consolidation in peripheraldistribution. One patient experienced a pneumonitis flare aftercompleting a prednisone taper, which is responsive to a secondcourse of corticosteroids. Further investigations in largercohorts are needed to characterize the full spectrum of thisentity. Given the rapidly growing indications for immune

A B

C D

Figure 2.Chest CT images for case 2. A–D, axial(A–C) and sagittal (D) images of chestCT scan at 4 weeks of therapydemonstrated multifocal areas ofGGO, reticular opacities, andextensive consolidation in the left lungwith a peripheral distribution,demonstrating a COP pattern(arrows).

Cancer Immunol Res; 4(4) April 2016 Cancer Immunology Research292

Nishino et al.

on April 9, 2021. © 2016 American Association for Cancer Research. cancerimmunolres.aacrjournals.org Downloaded from

Published OnlineFirst February 10, 2016; DOI: 10.1158/2326-6066.CIR-15-0267

checkpoint inhibitors in a variety of tumor types, knowledge ofthe clinical and radiographic manifestations of drug-relatedpneumonitis is essential to maximizing the therapeutic benefitof these agents.

Disclosure of Potential Conflicts of InterestM.Nishino is a consultant/advisory boardmember for Bristol-Myers Squibb.

F.S. Hodi is a consultant/advisory board member for Genentech, Merck, andNovartis. M.M. Awad is a consultant/advisory board member for AstraZeneca,Genentech, and Merck. No potential conflicts of interest were disclosed by theother authors.

Authors' ContributionsConception and design: M. Nishino, H. Hatabu, F.S. Hodi, M.M. AwadDevelopment of methodology: M. Nishino, H. Hatabu, M.M. AwadAcquisition of data (provided animals, acquired and managed patients,provided facilities, etc.): M. Nishino, E.S. Chambers, C.R. Chong, S.W. Gray,J.P. Marcoux, F.S. Hodi, M.M. Awad

Analysis and interpretation of data (e.g., statistical analysis, biostatistics,computational analysis): M. Nishino, N.H. Ramaiya, H. Hatabu, F.S. Hodi,M.M. AwadWriting, review, and/or revision of the manuscript: M. Nishino,N.H. Ramaiya, S.W. Gray, J.P. Marcoux, H. Hatabu, P.A. J€anne, F.S. Hodi,M.M. AwadAdministrative, technical, or material support (i.e., reporting or organizingdata, constructing databases): F.S. Hodi, M.M. AwadStudy supervision: M.M. Awad

Grant SupportM. Nishino, was supported by 1K23CA157631 (NCI).The costs of publication of this article were defrayed in part by the

payment of page charges. This article must therefore be hereby markedadvertisement in accordance with 18 U.S.C. Section 1734 solely to indicatethis fact.

Received October 27, 2015; revised December 21, 2015; accepted January 4,2016; published OnlineFirst February 10, 2016.

References1. Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, et al.

Overall survival and long-term safety of nivolumab (Anti-ProgrammedDeath 1 Antibody, BMS-936558, ONO-4538) in patients with previouslytreated advancednon-small-cell lung cancer. J ClinOncol 2015;33:2004–12.

2. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al.Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2trial. Lancet Oncol 2015;16:908–18.

3. Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ,et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpointinhibitor, for patients with advanced, refractory squamous non-small-celllung cancer (CheckMate 063): A phase 2, single-arm trial. Lancet Oncol2015;16:257–65.

4. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimu-mab-refractory advanced melanoma: a randomised dose-comparisoncohort of a phase 1 trial. Lancet 2014;384:1109–17.

5. Topalian SL,Hodi FS, Brahmer JR,Gettinger SN, SmithDC,McDermottDF,et al. Safety, activity, and immune correlates of anti-PD-1 antibody incancer. N Engl J Med 2012;366:2443–54.

6. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, SharfmanWH, et al. Survival, durable tumor remission, and long-term safety inpatients with advanced melanoma receiving nivolumab. J Clin Oncol2014;32:1020–30.

7. Nishino M, Tirumani SH, Ramaiya NH, Hodi FS. Cancer immunotherapyand immune-related response assessment: the role of radiologists in thenew arena of cancer treatment. Eur J Radiol 2015;84:1259–68.

8. Brahmer J, Reckamp KL, Baas P, Crin�o L, Eberhardt WE, Poddubskaya E,et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015;373:123–35.

9. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al.Nivolumab versus docetaxel in advanced nonsquamous non-small-celllung cancer. N Engl J Med 2015;373:1627–39.

10. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al.Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl JMed 2015;372:2018–28.

11. Nishino M, Sholl LM, Hodi FS, Hatabu H, Ramaiya NH. Anti-PD-1-related pneumonitis during cancer immunotherapy. N Engl J Med 2015;373:288–90.

12. NishinoM, Boswell EN,HatabuH,Ghobrial IM, Ramaiya NH. Drug-relatedpneumonitis during mammalian target of rapamycin inhibitor therapy:radiographic pattern-based approach in Waldenström macroglobulinemiaas a paradigm. Oncologist 2015;20:1077–83.

13. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG,et al. An official American Thoracic Society/European Respiratory Societystatement: Update of the international multidisciplinary classification ofthe idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188:733–48.

14. Kim SJ, Lee KS, Ryu YH, Yoon YC, Choe KO, Kim TS, et al. Reversed halosign on high-resolution CT of cryptogenic organizing pneumonia: diag-nostic implications. AJR Am J Roentgenol 2003;180:1251–4.

15. Horvat TZ, Adel NG, Dang TO, Momtaz P, PostowMA, CallahanMK, et al.Immune-related adverse events, need for systemic immunosuppression,and effects on survival and time to treatment failure in patients withmelanoma treated with ipilimumab at Memorial Sloan Kettering CancerCenter. J Clin Oncol 2015;33:3193–8.

16. NishinoM,Cardarella S, Dahlberg SE, Araki T, LydonC, JackmanDM, et al.Interstitial lung abnormalities in treatment-naive advanced non-small-celllung cancer patients are associated with shorter survival. Eur J Radiol2015;84:998–1004.

www.aacrjournals.org Cancer Immunol Res; 4(4) April 2016 293

Anti–PD-1 Inhibitor–Related Pneumonitis in Lung Cancer

on April 9, 2021. © 2016 American Association for Cancer Research. cancerimmunolres.aacrjournals.org Downloaded from

Published OnlineFirst February 10, 2016; DOI: 10.1158/2326-6066.CIR-15-0267

2016;4:289-293. Published OnlineFirst February 10, 2016.Cancer Immunol Res   Mizuki Nishino, Emily S. Chambers, Curtis R. Chong, et al.   Cancer

Small Cell Lung−Related Pneumonitis in Non−PD-1 Inhibitor−Anti

  Updated version

  10.1158/2326-6066.CIR-15-0267doi:

Access the most recent version of this article at:

   

   

  Cited articles

  http://cancerimmunolres.aacrjournals.org/content/4/4/289.full#ref-list-1

This article cites 16 articles, 4 of which you can access for free at:

  Citing articles

  http://cancerimmunolres.aacrjournals.org/content/4/4/289.full#related-urls

This article has been cited by 13 HighWire-hosted articles. Access the articles at:

   

  E-mail alerts related to this article or journal.Sign up to receive free email-alerts

  Subscriptions

Reprints and

  .pubs@aacr.orgat

To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department

  Permissions

  Rightslink site. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC)

.http://cancerimmunolres.aacrjournals.org/content/4/4/289To request permission to re-use all or part of this article, use this link

on April 9, 2021. © 2016 American Association for Cancer Research. cancerimmunolres.aacrjournals.org Downloaded from

Published OnlineFirst February 10, 2016; DOI: 10.1158/2326-6066.CIR-15-0267