Vol 16, No 2 (2020)
Review paper
Published online: 2020-03-13

open access

Page views 937
Article views/downloads 696
Get Citation

Connect on Social Media

Connect on Social Media

Summary of immunotherapy efficacy ordered in accordance with drug reimbursement program in melanoma patients

Anna M Czarnecka12, Piotr Rutkowski1
Oncol Clin Pract 2020;16(2):56-68.


Nivolumab and pembrolizumab are monoclonal antibodies of the IgG4 class, which target the cell death receptor (PD-1) found on T cells. The binding of the anti-PD-1 drug to the receptor therefore prevents the inhibition of these T cells and increases the immune response against melanoma cells. Pembrolizumab and nivolumab monotherapy has similar efficacy, including PFS and OS. Nivolumab and pembrolizumab immunotherapy are effective regardless of the BRAF mutation status. Currently, the choice between nivolumab and pembrolizumab is primarily dependent on to the frequency of infusions (every 3 weeks for pembrolizumab vs. every 2 weeks for nivolumab or every 6 weeks vs. every 4 weeks). Based on the available data, it can be concluded that autoimmune disease is not an absolute contraindication to the use of immunotherapy, but close clinical monitoring of these patients and specialist consultations (e.g. rheumatologist, dermatologist) must be provided. Patients with severe autoimmune disease who are treated with biologicals or have a history of life-threatening autoimmune disease complications (e.g. severe Crohn’s disease) should not be qualified for immunotherapy, as opposed to patients with minimally symptomatic autoimmune disease (e.g., mild dermal psoriasis).

Article available in PDF format

View PDF Download PDF file


  1. Centanni M, Moes DJ, Trocóniz IF, et al. Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors. Clin Pharmacokinet. 2019; 58(7): 835–857.
  2. Ciążyńska M, et al. Nowe możliwości leczenia pacjentów z zaawansowanym czerniakiem skóry. Forum Dermatologicum. 2017; 3(2): 53–57.
  3. Rutkowski P, Wysocki PJ, et al. Wytyczne postępowania diagnostyczno-terapeutycznego. Czerniaki skóry. Onkol Prakt Klin Edu. 2019; 5(1): 1–20.
  4. Ziobro M, Cybulska-Stopa B. Uaktualnione wyniki badań KEYNOTE 001 oraz KEYNOTE 006 — ich wpływ na naszą wiedzę o immunoterapii czerniaka i praktykę kliniczną. Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory. 2018; 3(3): 170–174.
  5. Koseła-Paterczyk H, Rutkowski P. Niwolumab — perspektywy w leczeniu nowotworów złośliwych. Onkol Prakt Klin Edu. 2016; 2(2): 57–68.
  6. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015; 372(4): 320–330.
  7. Ascierto PA, Long GV, Robert C, et al. Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial. JAMA Oncol. 2019; 5(2): 187–194.
  8. Ribas A, Hamid O, Daud A, et al. Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. JAMA. 2016; 315(15): 1600–1609.
  9. Hamid O, Robert C, Daud A, et al. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019; 30(4): 582–588.
  10. Robert C, Ribas A, Schachter J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019; 20(9): 1239–1251.
  11. Carlino MS, Long GV, Schadendorf D, et al. Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. Eur J Cancer. 2018; 101: 236–243.
  12. Munhoz RR, Postow MA. Clinical Development of PD-1 in Advanced Melanoma. Cancer J. 2018; 24(1): 7–14.
  13. Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016; 13(8): 473–486.
  14. Larkin J, Lao CD, Urba WJ, et al. Efficacy and Safety of Nivolumab in Patients With BRAF V600 Mutant and BRAF Wild-Type Advanced Melanoma: A Pooled Analysis of 4 Clinical Trials. JAMA Oncol. 2015; 1(4): 433–440.
  15. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Abstract CT075: Overall survival (OS) results from a phase III trial of nivolumab (NIVO) combined with ipilimumab (IPI) in treatment-naïve patients with advanced melanoma (CheckMate 067). Clinical Trials. 2017.
  16. da Silveira Nogueira Lima JP, Georgieva M, Haaland B, et al. A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma. Cancer Med. 2017; 6(6): 1143–1153.
  17. Pasquali S, Hadjinicolaou AV, Chiarion Sileni V, et al. Systemic treatments for metastatic cutaneous melanoma. Cochrane Database Syst Rev. 2018; 2: CD011123.
  18. Atkins MB, Tarhini A, Rael M, et al. Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison. Immunotherapy. 2019; 11(7): 617–629.
  19. Ackerman A, Klein O, McDermott DF, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer. 2014; 120(11): 1695–1701.
  20. Ascierto PA, Simeone E, Sileni VC, et al. Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: data from the Italian cohort of the ipilimumab expanded access program. Cancer Invest. 2014; 32(4): 144–149.
  21. Kong BY, Carlino MS, Menzies AM. Biology and treatment of BRAF mutant metastatic melanoma. Melanoma Manag. 2016; 3(1): 33–45.
  22. Johnson DB, Pectasides E, Feld E, et al. Sequencing Treatment in BRAFV600 Mutant Melanoma: Anti-PD-1 Before and After BRAF Inhibition. J Immunother. 2017; 40(1): 31–35.
  23. Gangadhar TC, Schuchter LM. Broad Applicability of Nivolumab in Melanoma Regardless of BRAF Mutation Status. JAMA Oncol. 2015; 1(4): 427–428.
  24. Ma Q, Shilkrut M, Zhao Z, et al. Autoimmune comorbidities in patients with metastatic melanoma: a retrospective analysis of us claims data. BMC Cancer. 2018; 18(1): 145.
  25. Batko B, Stajszczyk M, Świerkot J, et al. Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide study. Arch Med Sci. 2019; 15(1): 134–140.
  26. Borzęcki A, Koncewicz A, Raszewska-Famielec M, et al. Epidemiology of psoriasis in the years 2008–2015 in Poland. Dermatology Review. 2018; 105(6): 693–700.
  27. Liberman AC, Budziñski ML, Sokn C, et al. Regulatory and Mechanistic Actions of Glucocorticoids on T and Inflammatory Cells. Front Endocrinol (Lausanne). 2018; 9: 235.
  28. Cutolo M, Sulli A, Pizzorni C, et al. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2001; 60(8): 729–735.
  29. Dhaked D, Prevention & management of side effects of systemic steroids. https://www.slideshare.net/daulatramdhaked/prevention-management-of-side-effects-of-systemic-steroids.
  30. Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017; 28(2): 368–376.
  31. Johnson DB, Sullivan RJ, Ott PA, et al. Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders. JAMA Oncol. 2016; 2(2): 234–240.
  32. Abdel-Wahab N, Shah M, Lopez-Olivo MA, et al. Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review. Ann Intern Med. 2018; 168(2): 121–130.
  33. Elias R, Giobbie-Hurder A, McCleary NJ, et al. Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer. 2018; 6(1): 26.
  34. Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017; 123(11): 1904–1911.
  35. Rutkowski P, Kiprian D, Dudzisz-Śledź M, et al. Management of brain metastases in melanoma . Oncol Clin Pract. 2019; 15(1): 51–61.
  36. Spalek M, Czarnecka AM. The role of radiotherapy in melanoma. Oncol Clin Pract. 2019; 15(3): 310–319.