Investigational New Drugs

, Volume 31, Issue 4, pp 1071–1077 | Cite as

Ipilimumab associated hepatitis: imaging and clinicopathologic findings

  • Kyung Won Kim
  • Nikhil H. Ramaiya
  • Katherine M. Krajewski
  • Jyothi P. Jagannathan
  • Sree Harsha Tirumani
  • Amitabh Srivastava
  • Nageatte Ibrahim
SHORT REPORT

Summary

Ipilimumab is a novel immunomodulator demonstrating promising efficacy in treatment of melanoma and other cancers. The clinical benefit from ipilimumab can be hampered by the immure-related adverse events (irAEs) caused by dysregulation of host immune system. Ipilimumab associated hepatitis is also an important irAE, however, there have been limited descriptions of its clinicopathologic and imaging characteristics. We aim to describe the clinicopathologic and imaging characteristics of 6 patients who were diagnosed as ipilimumab associated hepatitis during the ipilimumab treatment for melanoma. The clinical features of these patients were as follows: (1) severe cases with systemic symptoms and highly increased level of liver function tests (LFTs), and (2) mild asymptomatic cases with mildly increased level of LFTs. In severe cases with ALT >1,000 IU/L, imaging findings were characterized by mild hepatomegaly, periportal edema, and periportal lymphadenopathy, while mild cases showed normal imaging findings. This spectrum of imaging findings in our series was similar to that of common causes of acute hepatitis. Among 3 cases with pathologic specimen, two cases showed severe panlobular hepatitis with prominent perivenular infiltrate with endothelialitis, suggestive of predominant injury to hepatocytes, while the other case showed mild portal mononuclear infiltrate around proliferated bile ductules, suggestive of predominant injury to bile ducts. In summary, ipilimumab associated hepatitis may demonstrate variable imaging findings according to its clinical severity, and histologically may manifest either as a predominant injury to hepatocytes (acute hepatitis pattern) or as a predominant injury to bile ducts (biliary pattern).

Keywords

Ipilimumab Hepatitis Immune-related adverse events Imaging Pathology 

Notes

Conflict of interest

All authors have nothing to disclose.

References

  1. 1.
    Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. doi:10.1056/NEJMoa1003466 PubMedCrossRefGoogle Scholar
  2. 2.
    Hoos A, Ibrahim R, Korman A et al (2010) Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy. Semin Oncol 37(5):533–546. doi:10.1053/j.seminoncol.2010.09.015 PubMedCrossRefGoogle Scholar
  3. 3.
    O’Regan KN, Jagannathan JP, Ramaiya N, Hodi FS (2011) Radiologic aspects of immune-related tumor response criteria and patterns of immune-related adverse events in patients undergoing ipilimumab therapy. AJR Am J Roentgenol 197(2):W241–W246. doi:10.2214/AJR.10.6032 PubMedCrossRefGoogle Scholar
  4. 4.
    Weber JS, Kahler KC, Hauschild A (2012) Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. doi:10.1200/JCO.2012.41.6750
  5. 5.
    Di Giacomo AM, Biagioli M, Maio M (2010) The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. Semin Oncol 37(5):499–507. doi:10.1053/j.seminoncol.2010.09.007 PubMedCrossRefGoogle Scholar
  6. 6.
    Lyall A, Vargas HA, Carvajal RD, Ulaner G (2012) Ipilimumab-induced colitis on FDG PET/CT. Clin Nucl Med 37(6):629–630. doi:10.1097/RLU.0b013e318248549a PubMedCrossRefGoogle Scholar
  7. 7.
    Bronstein Y, Ng CS, Hwu P, Hwu WJ (2011) Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy. AJR Am J Roentgenol 197(6):W992–W1000. doi:10.2214/AJR.10.6198 PubMedCrossRefGoogle Scholar
  8. 8.
    Mortele KJ, Segatto E, Ros PR (2004) The infected liver: radiologic-pathologic correlation. Radiographics 24(4):937–955. doi:10.1148/rg.244035719 PubMedCrossRefGoogle Scholar
  9. 9.
    Kleiner DE, Berman D (2012) Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma. Dig Dis Sci 57(8):2233–2240. doi:10.1007/s10620-012-2140-5 PubMedCrossRefGoogle Scholar
  10. 10.
    Phan GQ, Yang JC, Sherry RM et al (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A 100(14):8372–8377. doi:10.1073/pnas.1533209100 PubMedCrossRefGoogle Scholar
  11. 11.
    O’Day SJ, Maio M, Chiarion-Sileni V et al (2010) Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol 21(8):1712–1717. doi:10.1093/annonc/mdq013 PubMedCrossRefGoogle Scholar
  12. 12.
    Chmiel KD, Suan D, Liddle C et al (2011) Resolution of severe ipilimumab-induced hepatitis after antithymocyte globulin therapy. J Clin Oncol 29(9):e237–e240. doi:10.1200/JCO.2010.32.2206 PubMedCrossRefGoogle Scholar
  13. 13.
    Cheever MA (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222:357–368. doi:10.1111/j.1600-065X.2008.00604.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kyung Won Kim
    • 1
    • 4
  • Nikhil H. Ramaiya
    • 1
  • Katherine M. Krajewski
    • 1
  • Jyothi P. Jagannathan
    • 1
  • Sree Harsha Tirumani
    • 1
  • Amitabh Srivastava
    • 2
  • Nageatte Ibrahim
    • 3
  1. 1.Department of ImagingDana-Farber Cancer Institute, Brigham and Women’s HospitalBostonUSA
  2. 2.Department of PathologyBrigham and Women’s HospitalBostonUSA
  3. 3.Department of OncologyDana-Farber Cancer Institute, Brigham and Women’s HospitalBostonUSA
  4. 4.Department of Radiology and Research Institute of RadiologyUniversity of Ulsan College of Medicine, Seoul Asan Medical CenterSeoulKorea

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