Kidney Cancer Journal 43 on CheckMate025 3.2%, per FDA label), but likely occurs fairly early in most patients (median time 10.6 weeks).2 As an acute tubulo-interstitial nephritis, it typically manifests with urinalysis demonstrating WBC, RBC, and WBC casts.25 Renal biopsy is rarely considered in RCC patients, the majority of which have solitary kidneys. In the event of severe acute kidney injury (AKI) checkpoint inhibitor therapy should immediately be discontinued, and corticosteroid therapy should be initiated promptly (e.g. 1mg/kg per day during 1 month followed by rapid tapering). The choice of withdrawing or reintroducing ICI should be decided upon after multidisciplinary discussion that includes defining the cancer status and its prognosis, the risk of end-stage renal disease account. Conclusion The advent of immune checkpoint inhibition in the treatment of RCC has helped to usher in a new era in managing this disease. With that, oncologists are facing a new spectrum of class specific toxicities, immune mediated adverse events Additional checkpoint inhibitors and numerous combination regimens are under investigation. Early data suggests that particularly the combination of two such immunomodulators may increase the incidence of immune related toxicities,26 highlighting the relevance of understanding and better managing these phenomena. As the clinical experience with immune checkpoint inhibitors grows, it is imperative to rapidly identify side effects and promptly initiate adequate management to improve outcomes while not detracting from the efficacy of checkpoint inhibition. Prospective data are still needed to further elucidate optimal strategies for specific immunosuppressive treatment; however, by adhering to established guidelines for such therapy, clinicians are more likely to realize the potential benefits of checkpoint blockade. References 1. Motzer RJ, Sharma P, McDermott, D, et al. CheckMate 025 phase III trial: Outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC). J Clin Oncol. 34;2016; (suppl 2S) Abstract 498. 2. Plimack ER, et al. 15th Intl Kidney Cancer Symposium. Nov 2016, Miami, FL. 3. Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol. 2015;33:1430-1437. 4. Weber JS, Hodi FS, Wolchok JD, et al. Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. J Clin. Oncol. 2017;35:785-792. 5. McDermott DF, Motzer RJ, Atkins MB, et al. Long-term overall survival (OS) with nivolumab in previ- ously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies. Presented at: the 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL. Abstract 4507. 6. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Can Treatment Rev. 2016;45:7-18. 7. Ryder M, Callahan M, Postow MA, et al. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer. 2014;21:371-381. 8. Postow MA. Managing immune checkpoint-blocking antibody side effects. 2015 ASCO Educational Book. asco.org/edbook. 76-83. 9. Ribas A, Kefford R, Marshall MA, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013;31:616-622. 10. Bernardo SG, Moskalenko M, Pan M, et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma. Melanoma Res. 2013;23:47-54. 11. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320-330. Epub 2014 Nov 16. 12. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134- 144. Epub 2013 Jun 2. 13. Pagès C, Gornet JM, Monsel G, Allez M, Bertheau P, Bagot M, et al. Ipilimumab induced acute severe colitis treated by infliximab. Melanoma Res 2013;23:227–30. 14. Kim KW, Ramaiya NH, Krajewski KM, et al. Ipilimumab associated hepatitis: imaging and clinicopathologic fındings. Invest New Drugs. 2013;31:1071-1077. 15. Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, doubleblind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 2010;11: 155-164. 16. Kleiner DE, Berman D. Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma. Dig Dis Sci. 2012;57: 2233-2240. 17. FDA prescribing information for nivolumab. Reference ID: 3932569 -FDAhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2016/ 125554s0 19lbl.pdf. 18. Osorio JC, Ni A, Chaft JE, et al. Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-smallcell lung cancer. Ann Oncol. 2017;28:583-589. 19. Blansfıeld JA, Beck KE, Tran K, et al. Cytotoxic T-lymphocyte associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother. 2005; 28:593-598. 20.Dillard T, Yedinak CG, Alumkal J, et al. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune-related adverse events across a spectrum of cancer subtypes. Pituitary. 2010;13: 29-38. 21. Sarnaik AA, Yu B, Yu D, et al. Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefıt in patients with resected high-risk stage IIIc/IV melanoma. Clin Cancer Res. 2011;17:896-906. 22. Iwama S, De Remigis A, Callahan MK, et al. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014;6:230ra45. 23. Topalian SL, SznolM,McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020-1030. 24. Naidoo J, Wang X, Woo KM, et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2017;35:709-717. 25. Cortazar FB, Marrone KA, Troxell ML, et al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int. 2016 Sep;90(3):638-47. 26. Hammers HJ, Plimack ER, Infante JR, et al. Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). ASCO Meeting Abstracts. 2014;32(15_suppl):4504. http://meeting.ascopubs.org/cgi/content/ abstract/32/15_ suppl/4504. KCJ
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