Onkologie. 2022:16(1):10-15 | DOI: 10.36290/xon.2022.002

Adverse effects of combination immunotherapy in renal cancer, lung cancer, and melanoma

Jindřich Kopecký, Ondřej Kubeček, Aneta Kyllarová, Peter Priester
Klinika onkologie a radioterapie, LF a FN Hradec Králové

Over the last decade, immunotherapy has been implemented into therapeutic algorithms of various solid tumors including melanoma, renal cancer (RCC) and non-small cell lung cancer (NSCLC). Immunotherapy with checkpoint inhibitors can be administered as both monotherapy or in combination with another checkpoint inhibitor. However, the risk of immune-related adverse events (irAE) becomes relevant in combined immunotherapy. The growing number of tumors being treated with immunotherapy rises a question whether there are differences across various tumors in terms of irAR incidence and severity. The aim of this article is to address these issues.

Keywords: immunotherapy, malignant melanoma, kidney cancer, lung cancer, nivolumab, ipilimumab, side effects.

Published: February 22, 2022  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Kopecký J, Kubeček O, Kyllarová A, Priester P. Adverse effects of combination immunotherapy in renal cancer, lung cancer, and melanoma. Onkologie. 2022;16(1):10-15. doi: 10.36290/xon.2022.002.
Download citation

References

  1. Elkord E, Alcantar-Orozco EM, Dovedi SJ, et al. T regulatory cells in cancer: recent advances and therapeutic potential. Expert Opin Biol Ther. 2010;10(11):1573-1586. Go to original source... Go to PubMed...
  2. Atzpodien J, Kirchner H, Rebmann U, et al. Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer. 2006;95(4):463-469. Go to original source... Go to PubMed...
  3. Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3(5):541-547. Go to original source... Go to PubMed...
  4. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. Go to original source... Go to PubMed...
  5. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23-34. Go to original source... Go to PubMed...
  6. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521-2532. Go to original source... Go to PubMed...
  7. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723. Go to original source... Go to PubMed...
  8. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1803-1813. Go to original source... Go to PubMed...
  9. 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(2):123-135. Go to original source... Go to PubMed...
  10. 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(17):1627-1639. Go to original source... Go to PubMed...
  11. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2019;381(16):1535-1546. Go to original source... Go to PubMed...
  12. Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20(10):1370-1385. Go to original source... Go to PubMed...
  13. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2019;381(21):2020-2031. Go to original source... Go to PubMed...
  14. Larkin J, Hodi FS, and Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(13):1270-1271. Go to original source...
  15. Peggs KS, Quezada SA, Korman AJ, and Allison JP. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol. 2006;18(2):206-213. Go to original source... Go to PubMed...
  16. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015-3029. Go to original source... Go to PubMed...
  17. McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013;2(5):662-673. Go to original source... Go to PubMed...
  18. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14):1277-1290. Go to original source... Go to PubMed...
  19. Ascierto P, Del Vecchio M, and Robert C. Overall survival (OS) and safety results from a phase 3 trial of ipilimumab (IPI) at 3 mg/kg vs 10 mg/kg in patients with metastatic melanoma. In European Society for Medical Oncology (ESMO) 2016 Congress. 2016:Copenhagen, Denmark. Go to original source...
  20. Weber JS, Kahler KC, and Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):2691-2697. Go to original source... Go to PubMed...
  21. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454. Go to original source... Go to PubMed...
  22. Khoja L, Day D, Wei-Wu Chen T, et al. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol. 2017;8(10):2377-2385. Go to original source... Go to PubMed...
  23. Berner F, Bomze D, Diem S, et al. Association of Checkpoint Inhibitor-Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non-Small Cell Lung Cancer. JAMA Oncol. 2019;5(7):1043-1047. Go to original source... Go to PubMed...
  24. Willemsen M, Melief CJM, Bekkenk MW, and Luiten RM. Targeting the PD-1/PD-L1 Axis in Human Vitiligo. Front Immunol. 2020;11:579022. Go to original source... Go to PubMed...
  25. Lebbé C, Meyer N, Mortier L, et al. Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial. J Clin Oncol. 2019;37(11):867-875. Go to original source... Go to PubMed...
  26. Hommes JW, Verheijden RJ, Suijkerbuijk KPM, Hamann D. Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events-A Comprehensive Review. Front Oncol. 2020;10:585311. Go to original source... Go to PubMed...
  27. Teulings HE, Limpens J, Jansen SN, et al. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. J Clin Oncol. 2015;33(7):773-781. Go to original source... Go to PubMed...
  28. Fujisawa Y, Yoshino K, Otsuka A, et al. Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab: Analysis of 60 Japanese patients. J Dermatol Sci. 2018;89(1):60-66. Go to original source... Go to PubMed...
  29. 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(7):785-792. Go to original source... Go to PubMed...
  30. Haratani K, Hayashi H, Chiba Y, et al. Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non-Small-Cell Lung Cancer. JAMA Oncol. 2018;4(3):374-378. Go to original source... Go to PubMed...
  31. Ishihara H, Takagi T, Kondo T, et al. Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab. Urol Oncol. 2019;37(6):355.e21-355.e29. Go to original source... Go to PubMed...
  32. Xing P, Zhang F, Wang G, et al. Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis. J Immunother Can­cer. 2019;7(1):341. Go to original source... Go to PubMed...
  33. Fiala O, Sorejs O, Sustr J, et al. Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors. Anticancer Res 2020;40(3):1219-1227. Go to original source... Go to PubMed...
  34. Ascierto PA, Del Vecchio M, Robert C, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18(5):611-622. Go to original source... Go to PubMed...
  35. Agrawal S, Feng Y, Roy A, et al. Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy. Journal for immunotherapy of can­cer. 2016;4:72-72. Go to original source... Go to PubMed...




Oncology

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.