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Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma

  • Authors:
    • Francesca Morgese
    • Valeria Cognigni
    • Laura Scortichini
    • Nicoletta Ranallo
    • Valentina Lunerti
    • Antonella Migliore
    • Francesca Tronconi
    • Rossana Berardi
  • View Affiliations / Copyright

    Affiliations: Oncology Clinic, Polytechnic University of Marche, United Hospitals of Ancona, I‑60126 Ancona, Italy, Osteoncology and Rare Tumors Center, IRCCS Romagna Scientific Institute for Cancer Research and Care ‘Dino Amadori’, I‑47014 Meldola, Italy
  • Article Number: 2
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    Published online on: November 23, 2022
       https://doi.org/10.3892/mco.2022.2598
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Abstract

In recent years, BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi), together with immune checkpoint inhibitors (ICIs), have changed the therapeutic strategy of cutaneous melanoma, both in adjuvant and metastatic settings. These inhibitors have significantly improved the clinical outcome for patients with melanoma, including in both BRAF‑mutated and BRAF‑wild type disease. Some preclinical and clinical studies have revealed that BRAFi and MEKi are able to influence T‑ and B‑cell activation, and to modulate immune system activation within the tumor microenvironment. Dabrafenib and trametinib have been shown to enhance the expression of melanoma antigens on BRAF‑mutated cells, and to favor both a cytotoxic and immune response against melanoma cells. Thereby, the present study described a case series of five women treated with BRAFi and MEKi, in both adjuvant and metastatic settings, that experienced potential immune‑related adverse events. In particular, these patients exhibited sarcoidosis, mesenteric panniculitis, lymphocytic colitis and neuropathy of phrenic nerve. Considering that T and B cells are responsible for immune‑related adverse events, as observed in patients treated with ICIs, the present study suggested a possible role of BRAFi and MEKi as triggers of immune system activation and subsequent immune‑related toxicities.
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1 

Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph R, Weber JS, et al: Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 30:582–588. 2019.PubMed/NCBI View Article : Google Scholar

2 

Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, Chiarion Sileni V, Schachter J, Garbe C, Bondarenko I, et al: Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 381:626–636. 2019.PubMed/NCBI View Article : Google Scholar

3 

Kuske M, Westphal D, Wehner R, Schmitz M, Beissert S, Praetorius C and Meier F: Immunomodulatory effects of BRAF and MEK inhibitors: Implications for melanoma therapy. Pharmacol Res. 136:151–159. 2018.PubMed/NCBI View Article : Google Scholar

4 

Welsh SJ and Corrie PG: Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 7:122–136. 2015.PubMed/NCBI View Article : Google Scholar

5 

Lheure C, Kramkimel N, Franck N, Laurent-Roussel S, Carlotti A, Queant A, Goldwasser F, Avril MF and Dupin N: Sarcoidosis in patients treated with vemurafenib for metastatic melanoma: A paradoxical autoimmune activation. Dermatology. 231:378–384. 2015.PubMed/NCBI View Article : Google Scholar

6 

Tijtgat J, Schwarze JK, Awada G, Neyns B and Aspeslagh S: Sarcoid-like reaction in a BRAF V600E-mutated metastatic melanoma patient during treatment with BRAF/MEK-targeted therapy. Melanoma Res. 31:272–276. 2021.PubMed/NCBI View Article : Google Scholar

7 

Gouveris P, Zouki DN, Sarris EG, Kolilekas L, Tryfonopoulos D, Papaxoinis G and Demiri S: Melanoma and sarcoidosis in patients receiving or not antineoplastic therapy. Case Rep Oncol. 14:1059–1065. 2021.PubMed/NCBI View Article : Google Scholar

8 

Boutros A, Schiavi C, Cecchi F, Spagnolo F, Guadagno A, Tanda ET, Giusti F, Murdaca G and Queirolo P: Case report: Immune-related toxicity during adjuvant treatment with BRAF Plus MEK inhibitors in a melanoma patient. Front Immunol. 11(579523)2020.PubMed/NCBI View Article : Google Scholar

9 

Ben-Betzalel G, Baruch EN, Boursi B, Steinberg-Silman Y, Asher N, Shapira-Frommer R, Schachter J and Markel G: Possible immune adverse events as predictors of durable response to BRAF inhibitors in patients with BRAF V600-mutant metastatic melanoma. Eur J Cancer. 101:229–235. 2018.PubMed/NCBI View Article : Google Scholar

10 

Klein SL and Flanagan KL: Sex differences in immune responses. Nat Rev Immunol. 16:626–638. 2016.PubMed/NCBI View Article : Google Scholar

11 

Unger JM, Vaidya R, Albain KS, LeBlanc M, Minasian LM, Gotay CC, Henry NL, Fisch MJ, Lee SM, Blanke CD and Hershman DL: Sex differences in risk of severe adverse events in patients receiving immunotherapy, targeted therapy, or chemotherapy in cancer clinical trials. J Clin Oncol. 40:1474–1486. 2022.PubMed/NCBI View Article : Google Scholar

12 

van der Kooij MK, Dekkers OM, Aarts MJB, van den Berkmortel FWPJ, Boers-Sonderen MJ, de Groot JWB, Hospers GAP, Piersma D, van Rijn RS, Suijkerbuijk KPM, et al: Sex-based differences in treatment with immune checkpoint inhibition and targeted therapy for advanced melanoma: A nationwide cohort study. Cancers (Basel). 13(4639)2021.PubMed/NCBI View Article : Google Scholar

13 

Jing Y, Zhang Y, Wang J, Li K, Chen X, Heng J, Gao Q, Ye Y, Zhang Z, Liu Y, et al: Association between sex and immune-related adverse events during immune checkpoint inhibitor therapy. J Natl Cancer Inst. 113:1396–1404. 2021.PubMed/NCBI View Article : Google Scholar

14 

Iannuzzi MC, Rybicki BA and Teirstein AS: Sarcoidosis. N Engl J Med. 357:2153–2165. 2007.PubMed/NCBI View Article : Google Scholar

15 

Hussein MRA and Abdelwahed SR: Mesenteric panniculitis: An update. Expert Rev Gastroenterol Hepatol. 9:67–78. 2015.PubMed/NCBI View Article : Google Scholar

16 

Storr MA: Microscopic colitis: Epidemiology, pathophysiology, diagnosis and current management-an update 2013. ISRN Gastroenterol. 2013(352718)2013.PubMed/NCBI View Article : Google Scholar

17 

Wang M, Zadeh S, Pizzolla A, Thia K, Gyorki DE, McArthur GA, Scolyer RA, Long G, Wilmott JS, Andrews MC, et al: Characterization of the treatment-naive immune microenvironment in melanoma with BRAF mutation. J Immunother Cancer. 10(e004095)2022.PubMed/NCBI View Article : Google Scholar

18 

Steinberg SM, Zhang P, Malik BT, Boni A, Shabaneh TB, Byrne KT, Mullins DW, Brinckerhoff CE, Ernstoff MS, Bosenberg MW and Turk MJ: BRAF inhibition alleviates immune suppression in murine autochthonous melanoma. Cancer Immunol Res. 2:1044–1050. 2014.PubMed/NCBI View Article : Google Scholar

19 

Ho PC, Meeth KM, Tsui YC, Srivastava B, Bosenberg MW and Kaech SM: Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNγ. Cancer Res. 74:3205–3217. 2014.PubMed/NCBI View Article : Google Scholar

20 

Hu-Lieskovan S, Mok S, Homet Moreno B, Tsoi J, Robert L, Goedert L, Pinheiro EM, Koya RC, Graeber TG, Comin-Anduix B and Ribas A: Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma. Sci Transl Med. 7(279ra41)2015.PubMed/NCBI View Article : Google Scholar

21 

Jung T, Haist M, Kuske M, Grabbe S and Bros M: Immunomodulatory properties of BRAF and MEK inhibitors used for melanoma therapy-paradoxical ERK activation and beyond. Int J Mol Sci. 22(9890)2021.PubMed/NCBI View Article : Google Scholar

22 

Ascierto PA and Dummer R: Immunological effects of BRAF+MEK inhibition. Oncoimmunology. 7(e1468955)2018.PubMed/NCBI View Article : Google Scholar

23 

Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P and Scolyer RA: Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 18:1386–1394. 2012.PubMed/NCBI View Article : Google Scholar

24 

Liu L, Mayes PA, Eastman S, Shi H, Yadavilli S, Zhang T, Yang J, Seestaller-Wehr L, Zhang SY, Hopson C, et al: The BRAF and MEK inhibitors dabrafenib and trametinib: Effects on immune function and in combination with immunomodulatory antibodies targeting PD-1, PD-L1, and CTLA-4. Clin Cancer Res. 21:1639–1651. 2015.PubMed/NCBI View Article : Google Scholar

25 

Vella LJ, Andrews MC, Pasam A, Woods K, Behren A and Cebon JS: The kinase inhibitors dabrafenib and trametinib affect isolated immune cell populations. Oncoimmunology. 3(e946367)2014.PubMed/NCBI View Article : Google Scholar

26 

Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, Mitra D, Boni A, Newton LP, Liu C, et al: BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 19:1225–1231. 2013.PubMed/NCBI View Article : Google Scholar

27 

Jiang X, Zhou J, Giobbie-Hurder A, Wargo J and Hodi FS: The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res. 19:598–609. 2013.PubMed/NCBI View Article : Google Scholar

28 

Dummer R, Brase JC, Garrett J, Campbell CD, Gasal E, Squires M, Gusenleitner D, Santinami M, Atkinson V, Mandalà M, et al: Adjuvant dabrafenib plus trametinib versus placebo in patients with resected, BRAFV600-mutant, stage III melanoma (COMBI-AD): Exploratory biomarker analyses from a randomised, phase 3 trial. Lancet Oncol. 21:358–372. 2020.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Morgese F, Cognigni V, Scortichini L, Ranallo N, Lunerti V, Migliore A, Tronconi F and Berardi R: Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma. Mol Clin Oncol 18: 2, 2023.
APA
Morgese, F., Cognigni, V., Scortichini, L., Ranallo, N., Lunerti, V., Migliore, A. ... Berardi, R. (2023). Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma. Molecular and Clinical Oncology, 18, 2. https://doi.org/10.3892/mco.2022.2598
MLA
Morgese, F., Cognigni, V., Scortichini, L., Ranallo, N., Lunerti, V., Migliore, A., Tronconi, F., Berardi, R."Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma". Molecular and Clinical Oncology 18.1 (2023): 2.
Chicago
Morgese, F., Cognigni, V., Scortichini, L., Ranallo, N., Lunerti, V., Migliore, A., Tronconi, F., Berardi, R."Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma". Molecular and Clinical Oncology 18, no. 1 (2023): 2. https://doi.org/10.3892/mco.2022.2598
Copy and paste a formatted citation
x
Spandidos Publications style
Morgese F, Cognigni V, Scortichini L, Ranallo N, Lunerti V, Migliore A, Tronconi F and Berardi R: Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma. Mol Clin Oncol 18: 2, 2023.
APA
Morgese, F., Cognigni, V., Scortichini, L., Ranallo, N., Lunerti, V., Migliore, A. ... Berardi, R. (2023). Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma. Molecular and Clinical Oncology, 18, 2. https://doi.org/10.3892/mco.2022.2598
MLA
Morgese, F., Cognigni, V., Scortichini, L., Ranallo, N., Lunerti, V., Migliore, A., Tronconi, F., Berardi, R."Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma". Molecular and Clinical Oncology 18.1 (2023): 2.
Chicago
Morgese, F., Cognigni, V., Scortichini, L., Ranallo, N., Lunerti, V., Migliore, A., Tronconi, F., Berardi, R."Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma". Molecular and Clinical Oncology 18, no. 1 (2023): 2. https://doi.org/10.3892/mco.2022.2598
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