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Frequency and imaging features of abdominal immune-related adverse events in metastatic lung cancer patients treated with PD-1 inhibitor

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Abstract

Purpose

To investigate the frequency and imaging features of radiographically evident abdominal immune-related adverse events (irAEs) in patients with metastatic non-small-cell lung cancer (NSCLC) treated with PD-1 inhibitors.

Methods

This retrospective study included 137 patients with metastatic NSCLC treated with PD-1 inhibitor nivolumab monotherapy (75 women; median age: 65 years), who had a baseline CT and at least one follow-up abdomen CT during therapy. Baseline and all follow-up abdominal CTs performed for monitoring of nivolumab therapy were reviewed to identify the organ-specific abdominal irAEs including colitis/enteritis, hepatitis, biliary toxicity, pancreatitis, nephritis, sarcoid-like reaction, and pancreatic and adrenal atrophy. Their frequency and imaging features were described.

Results

Eighteen (13%) patients had radiologically identified abdominal irAEs (median 2.1 months after starting nivolumab; interquartile range 1.17–5.83 months); 16 patients developed enteritis/colitis (12 pancolitis, two segmental colitis, one enterocolitis, one enteritis), two hepatitis, one adrenalitis. One patient with hepatitis also developed colitis/enteritis. Radiographic abdominal irAE occurred after nivolumab therapy was discontinued in six patients before any subsequent therapy was started. IrAEs prompted nivolumab interruption and treatment with steroids in four patients (three colitis/enteritis, one hepatitis). Most common CT features of colitis/enteritis included mesenteric hyperemia (n = 15), bowel wall thickening (n = 13), mucosal hyperenhancement (n = 10), and fluid-filled colon (n = 9).

Conclusion

Abdominal irAEs were detected on CT in 13% of NSCLC patients treated with nivolumab, and colitis, in the pancolitis form, was the most common irAE. Given the expanding role of immunotherapy, radiologists should be aware of the frequency and imaging manifestations of abdominal irAEs and the impact on patient management.

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References

  1. Opdivo. Full prescribing information. U. S. Food and Drug Administration/Center for Drug Evaluation and Research.https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125554s055lbl.pdf. Published December 2014. Updated December 2017. Accessed September 21, 2018.

  2. D'Angelo SP, Mahoney MR, Van Tine BA, et al (2018) Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol 19(3):416-426.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fife BT, Pauken KE, Eagar TN, et al (2009) Interactions between programmed death-1 and programmed death ligand-1 promote tolerance by blocking the T cell receptor-induced stop signal. Nat immunol 10(11):1185-1192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dong H, Strome SE, Salomao DR, et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793-800.

    Article  CAS  PubMed  Google Scholar 

  5. Francisco LM, Salinas VH, Brown KE, et al (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 206(13):3015-3029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mekki A, Dercle L, Lichtenstein P, et al (2018) Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1. Eur J Cancer 96:91-104.

    Article  CAS  PubMed  Google Scholar 

  7. Wang PF, Chen Y, Song S-Y, et al (2017) Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. Front Pharmacol 8:730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Carbone DP, Reck M, Paz-Ares L, et al (2017) First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med 376:2415-2426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nishino M, Tirumani SH, Ramaiya NH, Hodi FS (2015) Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment. Eur J Radiol 84(7):1259-1268.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tirumani SH, Ramaiya NH, Keraliya A, et al (2015) Radiographic Profiling of Immune-related Adverse Events in Advanced Melanoma Patients Treated With Ipilimumab. Cancer Immunol Res3(10):1185-1192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nishino M, Hatabu H, Hodi FS, Ramaiya NH. Drug-Related Pneumonitis in the Era of Precision Cancer Therapy. JCO Precision Oncology 2017:1,1-12. https://doi.org/10.1200/PO.17.00026. Published May 26, 2017. Accessed September 21, 2018.

    Article  Google Scholar 

  12. Lipson EJ, Sharfman WH, Drake CG, et al (2013) Durable Cancer Regression Off-treatment and Effective Re-induction Therapy with an Anti-PD-1 Antibody. Clin Cancer Res 19(2):462-468.

    Article  CAS  PubMed  Google Scholar 

  13. Puzanov I, Diab A, Abdallah K, et al (2017) Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 5:95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim KW, Ramaiya NH, Krajewski KM, et al (2013) Ipilimumab-associated colitis: CT findings. AJR Am J Roentgenol 200:W468-474.

    Article  PubMed  Google Scholar 

  15. Kim KW, Ramaiya NH, Krajewski KM, et al (2013) Ipilimumab associated hepatitis: imaging and clinicopathologic findings. Invest New Drugs.31:1071–1077.

    Article  CAS  PubMed  Google Scholar 

  16. Raad RA, Pavlick A, Kannan R, Friedman KP (2015) Ipilimumab-induced hepatitis on 18F-FDG PET/CT in a patient with malignant melanoma. Clin Nucl Med40(3):258-259.

    Article  PubMed  Google Scholar 

  17. Linguraru MG, Sandberg JK, Jones EC, Petrick N, Summers RM (2012) Assessing hepatomegaly: automated volumetric analysis of the liver. Acad Radiol 19(5):588-598.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hamer OW, Aguirre DA, Casola G, et al (2006) Fatty liver: imaging patterns and pitfalls. Radiographics 26 (6): 1637-1653.

    Article  PubMed  Google Scholar 

  19. Alabed YZ, Aghayev A, Sakellis C, Van den Abbeele AD (2015) Pancreatitis Secondary to Anti-Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT. Clin Nucl Med 40(11):e528-529.

    Article  PubMed  Google Scholar 

  20. Sampson JH, Vlahovic G, Sahebjam S et al (2015) Preliminary safety and activity of nivolumab and its combination with ipilimumab in recurrent glioblastoma (GBM): CHECKMATE-143. J Clin Oncol 2015;33:15,suppl3010.

    Article  Google Scholar 

  21. Forde PM, Rock K, Wilson G, O'Byrne KJ (2012) Ipilimumab-induced immune-related renal failure--a case report. Anticancer Res32(10):4607-4608.

    PubMed  Google Scholar 

  22. Bélissant O Jr1, Guernou M, Rouvier P, Compain C, Bonardel G (2015) IgG4-Related Tubulointerstitial Nephritis Pattern in 18F-FDG PET/CT. Clin Nucl Med 40(10):808-809.

    Article  PubMed  Google Scholar 

  23. Min L, Ibrahim N (2013) Ipilimumab-induced autoimmune adrenalitis. Lancet Diabetes Endocrinol 1(3):e15.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bacanovic S; Burger IA; Stolzmann P; Hafner J; Huellner MW (2015) Ipilimumab induced adrenalitis: a possible pitfall in 18F-FDG-PET/CT. Clin Nucl Med 40(11):e518-e519.

    Article  PubMed  Google Scholar 

  25. Cheshire SC, Board RE, Lewis AR, Gudur LD, Dobson MJ (2018) Pembrolizumab-induced Sarcoid-like Reactions during Treatment of Metastatic Melanoma. Radiology14:180572.

    Google Scholar 

  26. Ryder M, Callahan M, Postow MA, Wolchok J, Fagin JA (2014) Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer 21(2):371-381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hoadley A, Sandanayake N, Long GV (2017) Atrophic exocrine pancreatic insufficiency associated with anti-PD1 therapy. Ann Oncol 28(2):434-435.

    CAS  PubMed  Google Scholar 

  28. Masuda A, Shiomi H, Matsuda T, et al (2014) The relationship between pancreatic atrophy after steroid therapy and diabetes mellitus in patients with autoimmune pancreatitis. Pancreatol14(5):361-365.

    Article  CAS  Google Scholar 

  29. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Bethesda, MD: Department of Health and Human Services; 2017. Available at: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Published March 1, 2018. Accessed Sept 21, 2018.

  30. Horn L, Spigel DR, Vokes EE, et al (2017) Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057). J Clin Oncol 35(35):3924-3933.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dougan M (2017) Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract. Front Immunol 8:1547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Thoeni RF, Cello JP (2006) CT imaging of colitis. Radiology 240(3):623-38.

    Article  PubMed  Google Scholar 

  33. Shinagare AB, Steele E, Braschi-Amirfarzan M, Tirumani SH, Ramaiya NH (2016) Sunitinib-associated Pancreatic Atrophy in Patients with Gastrointestinal Stromal Tumor: A Toxicity with Prognostic Implications Detected at Imaging. Radiology 281(1):140-149.

    Article  PubMed  Google Scholar 

  34. Shinagare AB, Guo M, Hatabu H, et al (2011) Incidence of pulmonary embolism in oncologic outpatients at a tertiary cancer center. Cancer 117(16):3860-3866.

    Article  PubMed  Google Scholar 

  35. Chen TW, Razak AR, Bedard PL, Siu LL, Hansen AR (2015) A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors. Ann Oncol 26(9):1824-1829.

    Article  CAS  PubMed  Google Scholar 

  36. Nishino M, Ramaiya NH, Awad MM, et al (2016) PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course. Clin Cancer Res 22(24):6051-6060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nishino M, Chambers ES, Chong CR, et al (2016) Anti–PD-1 inhibitor–related pneumonitis in non–small cell lung cancer. Cancer Immunol Res 4(4):289-293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nishino M, Sholl LM, Hodi FS, Hatabu H, Ramaiya NH (2015) Anti-PD-1-Related Pneumonitis during Cancer Immunotherapy. N Engl J Med 373(3):288-290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Carpenter KJ, Murtagh RD, Lilienfeld H, Weber J, Murtagh FR (2009) Ipilimumab-induced hypophysitis: MR imaging findings. AJNR Am J Neuroradiol 30(9):1751-1753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Francesco Alessandrino, Mizuki Nishino, Sree Harsha Tirumani & Atul B. Shinagare

  2. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Francesco Alessandrino, Sonia Sahu, Mizuki Nishino, Sree Harsha Tirumani & Atul B. Shinagare

  3. Department of Medical Oncology and Department of Medicine, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Anika E. Adeni & Mark M. Awad

Authors
  1. Francesco Alessandrino
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  2. Sonia Sahu
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  3. Mizuki Nishino
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  4. Anika E. Adeni
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  5. Sree Harsha Tirumani
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  6. Atul B. Shinagare
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Corresponding author

Correspondence to Atul B. Shinagare.

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Conflict of interest

Francesco Alessandrino, MD: no conflict of interests. Sonia Sahu, MD: no conflict of interests. Mizuki Nishino MD, MPH Consultant to Bristol-Myers Squibb, Toshiba Medical Systems, WorldCare Clinical, Daiichi Sankyo; Research grant from Merck Investigator Studies Program, Toshiba Medical Systems, AstraZeneca; Honorarium from Bayer and Roche. The investigator, M.N., was supported by 1R01CA203636 (NCI). Anika E. Adeni: no conflict of interests. Sree Harsha Tirumani, MD: no conflict of interests. Atul B. Shinagare, MD: Consultant, Arog Pharmaceuticals. Mark Awad, MD, PhD: Consultant Bristol-Myers Squibb, Merck, Genentech, AstraZeneca. Research funding from Bristol-Myers Squibb.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Alessandrino, F., Sahu, S., Nishino, M. et al. Frequency and imaging features of abdominal immune-related adverse events in metastatic lung cancer patients treated with PD-1 inhibitor. Abdom Radiol 44, 1917–1927 (2019). https://doi.org/10.1007/s00261-019-01935-2

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