CONCLUSIONS

Checkpoint inhibitor-induced immune related hepatitis is a clinically significant toxicity for patients with GI cancer. All patients receiving therapy should be monitored closely and prompt recognition of hepatitis is essential to ensure that appropriate treatment is started in a timely manner. Clinicians should maintain a low threshold for working up and treating suspected immune hepatitis as delays can lead to permanent discontinuation of cancer therapy.

Acknowledgments

None.


Aravind Sanjeevaiah1,2, Thomas Kerr3, Muhammad Shaalan Beg1,2

1Division of Hematology and Medical Oncology, Department of Internal Medicine, 2Harold Simmons Comprehensive Cancer Center, 3Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, USA

Correspondence to: Muhammad Shaalan Beg, MD, MS. Division of Hematology/Oncology, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8852, USA. Email: Muhammad.Beg@UTSouthwestern.edu


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23.

2. Administration USFaD. Hematology/Oncology (Cancer) Approvals & Safety Notifications. 2017. Available online: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm279174.htm. Accessed 06/21/2017.

3. Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015;372:2509-20. 

4. Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 2016;17:717-26. 

5. Melero I, Sangro B, Yau TC, et al. Nivolumab dose escalation and expansion in patients with advanced hepatocellular carcinoma (HCC): The CheckMate 040 study. J Clin Oncol 2017;35:226. 

6. Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol 2016;34:2460-7. 

7. Pianko MJ, Liu Y, Bagchi S, et al. Immune checkpoint blockade for hematologic malignancies: a review. Stem Cell Investig 2017;4:32. 

8. O’Day SJ, Hamid O, Urba WJ. Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer 2007;110:2614-27. 

9. Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 2016;54:139-48. 

10. Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012;30:2691-7. 

11. Johncilla M, Misdraji J, Pratt DS, et al. Ipilimumab-associated Hepatitis: Clinicopathologic Characterization in a Series of 11 Cases. Am J Surg Pathol 2015;39:1075-84. 

12. Kim KW, Ramaiya NH, Krajewski KM, et al. Ipilimumab associated hepatitis: imaging and clinicopathologic findings. Invest New Drugs 2013;31:1071-7.

13. Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014;384:1109-17. 

14. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015;372:320-30.

15. Wang W, Lie P, Guo M, et al. Risk of hepatotoxicity in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis of published data. Int J Cancer 2017;141:1018-28.

16. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015;372:2006-17. 

17. Hammers H, Plimack ER, Infante JR, et al. Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). J Clin Oncol 2014;32:4504.

18. Ribas A, Hodi FS, Callahan M, et al. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med 2013;368:1365-6. 

19. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26. 

20. Champiat S, Dercle L, Ammari S, et al. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res 2017;23:1920-8.

21. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015;373:1627-39. 

22. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015;373:123-35.

23. Chmiel KD, Suan D, Liddle C, et al. Resolution of severe ipilimumab-induced hepatitis after antithymocyte globulin therapy. J Clin Oncol 2011;29:e237-40. 

24. Network NCC. Prevention and Treatment of Cancer-Related Infections. 2017. Available online: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 06/21/2017.

Source: Journal of Gastrointestinal Oncology.
Originally published February 2018.