Skip to main content
Erschienen in: Current Dermatology Reports 4/2023

30.08.2023 | HOT TOPIC

Incidence and Characteristics of Melanoma in Multiple Sclerosis Patients Treated With Fingolimod: A Systematic Review

verfasst von: Melinda Jiang, Lydia Lam, YiZhong Zhuang, Rudy Goh, Joshua G. Kovoor, Aashray K. Gupta, William B. Smith, Mark Slee, Stephen Bacchi

Erschienen in: Current Dermatology Reports | Ausgabe 4/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The treatment of multiple sclerosis has been revolutionised by disease-modifying therapies including fingolimod. However, these treatments are immunosuppressive and may be associated with increased risk and severity of skin cancer including melanoma. The aim of this review was to identify and evaluate the existing evidence regarding this relationship to help guide future patient counselling and screening practices. This systematic review involved a systematic search of the databases PubMed, EMBASE and Cochrane library, which was performed in July 2022.

Recent Findings

The initial search strategy identified 1,457 studies, of which 19 fulfilled the inclusion criteria totalling 20,175 patients receiving fingolimod. In total, there were 141 cases of melanoma reported in patients receiving fingolimod. The reported melanomas were all cutaneous, there were no new cases of uveal or genitourinary mucosal melanoma reported. It is unclear whether duration of treatment with fingolimod affects melanoma risk, severity, recurrence rates, metastatic potential or outcome. Patient-related risk factors such as skin type, UV exposure, family history etc. were not reported in most studies. In most reports, patients who developed melanoma discontinued fingolimod. There were no reports of metastatic disease or death.

Summary

Multiple case reports, observational studies, pharmacovigilance studies and clinical trials have reported melanoma in MS patients receiving fingolimod. This literature review provides evidence to support the recommendation of screening for melanoma in patients receiving fingolimod. Prior to the commencement of fingolimod, patients should be screened for melanoma risk factors and be counselled accordingly.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.CrossRefPubMed Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.CrossRefPubMed
3.
Zurück zum Zitat Alping P, Askling J, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al. Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients. Ann Neurol. 2020;87(5):688–99.CrossRefPubMed Alping P, Askling J, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al. Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients. Ann Neurol. 2020;87(5):688–99.CrossRefPubMed
4.
Zurück zum Zitat Manni A, Direnzo V, Iaffaldano A, Di Lecce V, Tortorella C, Zoccolella S, et al. Gender differences in safety issues during Fingolimod therapy: Evidence from a real-life Relapsing Multiple Sclerosis cohort. Brain Behav. 2017;7(10): e00804.CrossRefPubMedPubMedCentral Manni A, Direnzo V, Iaffaldano A, Di Lecce V, Tortorella C, Zoccolella S, et al. Gender differences in safety issues during Fingolimod therapy: Evidence from a real-life Relapsing Multiple Sclerosis cohort. Brain Behav. 2017;7(10): e00804.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat White C, Alshaker H, Cooper C, Winkler M, Pchejetski D. The emerging role of FTY720 (Fingolimod) in cancer treatment. Oncotarget. 2016;7(17):23106–27.CrossRefPubMedPubMedCentral White C, Alshaker H, Cooper C, Winkler M, Pchejetski D. The emerging role of FTY720 (Fingolimod) in cancer treatment. Oncotarget. 2016;7(17):23106–27.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Herzinger T, Kleuser B, Schäfer-Korting M, Korting HC. Sphingosine-1-Phosphate Signaling and the Skin. Am J Clin Dermatol. 2007;8(6):329–36.CrossRefPubMed Herzinger T, Kleuser B, Schäfer-Korting M, Korting HC. Sphingosine-1-Phosphate Signaling and the Skin. Am J Clin Dermatol. 2007;8(6):329–36.CrossRefPubMed
7.
Zurück zum Zitat Hasan Ali O, Berner F, Ackermann CJ, Ring SS, Moulin A, Müller J, et al. Fingolimod and tumor-infiltrating lymphocytes in checkpoint-inhibitor treated cancer patients. Cancer Immunology, Immunotherapy. 2021;70(2):563–8.CrossRefPubMed Hasan Ali O, Berner F, Ackermann CJ, Ring SS, Moulin A, Müller J, et al. Fingolimod and tumor-infiltrating lymphocytes in checkpoint-inhibitor treated cancer patients. Cancer Immunology, Immunotherapy. 2021;70(2):563–8.CrossRefPubMed
9.
Zurück zum Zitat Berge LAM, Andreassen BK, Stenehjem JS, Heir T, Karlstad Ø, Juzeniene A, et al. Use of Immunomodulating Drugs and Risk of Cutaneous Melanoma: A Nationwide Nested Case-Control Study</p&gt. Clinical Epidemiology. 2020;12:1389–401.CrossRefPubMedPubMedCentral Berge LAM, Andreassen BK, Stenehjem JS, Heir T, Karlstad Ø, Juzeniene A, et al. Use of Immunomodulating Drugs and Risk of Cutaneous Melanoma: A Nationwide Nested Case-Control Study</p&gt. Clinical Epidemiology. 2020;12:1389–401.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Cordaro A, Dobbs TD, Gibson JA, Whitaker S, Whitaker IS. Skin cancer screening in organ transplant centres in the United Kingdom: a national survey. Eur J Dermatol. 2020;30(4):372–6.CrossRefPubMed Cordaro A, Dobbs TD, Gibson JA, Whitaker S, Whitaker IS. Skin cancer screening in organ transplant centres in the United Kingdom: a national survey. Eur J Dermatol. 2020;30(4):372–6.CrossRefPubMed
11.
Zurück zum Zitat Budde K, Schutz M, Glander P, Peters H, Waiser J, Liefeldt L, et al. FTY720 (fingolimod) in renal transplantation. Clin Transplant. 2006;20(Suppl 17):17–24.CrossRefPubMed Budde K, Schutz M, Glander P, Peters H, Waiser J, Liefeldt L, et al. FTY720 (fingolimod) in renal transplantation. Clin Transplant. 2006;20(Suppl 17):17–24.CrossRefPubMed
12.
Zurück zum Zitat Robinson CL, Guo M. Fingolimod (Gilenya) and melanoma. BMJ Case Rep. 2016;2016. Robinson CL, Guo M. Fingolimod (Gilenya) and melanoma. BMJ Case Rep. 2016;2016.
13.
Zurück zum Zitat Killestein J, Leurs CE, Hoogervorst ELJ, van Eijk J, Mostert JP, van den Eertwegh AJM, et al. Five cases of malignant melanoma during fingolimod treatment in Dutch patients with MS. Neurology. 2017;89(9):970–2.CrossRefPubMed Killestein J, Leurs CE, Hoogervorst ELJ, van Eijk J, Mostert JP, van den Eertwegh AJM, et al. Five cases of malignant melanoma during fingolimod treatment in Dutch patients with MS. Neurology. 2017;89(9):970–2.CrossRefPubMed
14.
Zurück zum Zitat Filoni A, Lospalluti L, Giudice G, Bonamonte D, Vestita M. Fingolimod and melanoma risk: is there sufficient evidence? Clin Exp Dermatol. 2017;42(4):427–8.CrossRefPubMed Filoni A, Lospalluti L, Giudice G, Bonamonte D, Vestita M. Fingolimod and melanoma risk: is there sufficient evidence? Clin Exp Dermatol. 2017;42(4):427–8.CrossRefPubMed
15.
Zurück zum Zitat Haebich G, Mughal A, Tofazzal N. Superficial spreading malignant melanoma in a patient on fingolimod therapy for multiple sclerosis. Clin Exp Dermatol. 2016;41(4):433–4.CrossRefPubMed Haebich G, Mughal A, Tofazzal N. Superficial spreading malignant melanoma in a patient on fingolimod therapy for multiple sclerosis. Clin Exp Dermatol. 2016;41(4):433–4.CrossRefPubMed
16.
Zurück zum Zitat Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10023):1075–84.CrossRefPubMed Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10023):1075–84.CrossRefPubMed
17.
Zurück zum Zitat Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.CrossRefPubMed Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.CrossRefPubMed
19.
Zurück zum Zitat Cohen JA, Khatri B, Barkhof F, Comi G, Hartung H-P, Montalban X, et al. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016;87(5):468-75. Cohen JA, Khatri B, Barkhof F, Comi G, Hartung H-P, Montalban X, et al. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016;87(5):468-75.
20.
Zurück zum Zitat Kappos L, Li DK, Stuve O, Hartung HP, Freedman MS, Hemmer B, et al. Safety and Efficacy of Siponimod (BAF312) in Patients With Relapsing-Remitting Multiple Sclerosis: Dose-Blinded, Randomized Extension of the Phase 2 BOLD Study. JAMA Neurol. 2016;73(9):1089–98.CrossRefPubMed Kappos L, Li DK, Stuve O, Hartung HP, Freedman MS, Hemmer B, et al. Safety and Efficacy of Siponimod (BAF312) in Patients With Relapsing-Remitting Multiple Sclerosis: Dose-Blinded, Randomized Extension of the Phase 2 BOLD Study. JAMA Neurol. 2016;73(9):1089–98.CrossRefPubMed
21.
Zurück zum Zitat Stamatellos VP, Rigas A, Stamoula E, Lallas A, Papadopoulou A, Papazisis G. S1P receptor modulators in Multiple Sclerosis: Detecting a potential skin cancer safety signal. Mult Scler Relat Disord. 2022;59: 103681.CrossRefPubMed Stamatellos VP, Rigas A, Stamoula E, Lallas A, Papadopoulou A, Papazisis G. S1P receptor modulators in Multiple Sclerosis: Detecting a potential skin cancer safety signal. Mult Scler Relat Disord. 2022;59: 103681.CrossRefPubMed
23.
24.
Zurück zum Zitat Pašić A. Wolff K, Johnson RA, Suurmond D, eds. Fitzpatrick´ s Color Atlas and Synopsis of Clinical Dermatology. New York: McGraw-Hill, 2005. One volume. Pages 1085, parts four, sections 33. ISBN 0-07-144019-4. Acta Dermatovenerologica Croatica. 2007;15(3):0. Pašić A. Wolff K, Johnson RA, Suurmond D, eds. Fitzpatrick´ s Color Atlas and Synopsis of Clinical Dermatology. New York: McGraw-Hill, 2005. One volume. Pages 1085, parts four, sections 33. ISBN 0-07-144019-4. Acta Dermatovenerologica Croatica. 2007;15(3):0.
25.
Zurück zum Zitat Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372: n160.CrossRefPubMedPubMedCentral Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372: n160.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Maniscalco GT, Morra VB, Florio C, Lus G, Tedeschi G, Cianfrani M, et al. Preliminary results of the FASM study, an on-going italian active pharmacovigilance project. Pharmaceuticals. 2020;13(12):1–18.CrossRef Maniscalco GT, Morra VB, Florio C, Lus G, Tedeschi G, Cianfrani M, et al. Preliminary results of the FASM study, an on-going italian active pharmacovigilance project. Pharmaceuticals. 2020;13(12):1–18.CrossRef
28.
Zurück zum Zitat Montalban X, Comi G, Antel J, O’Connor P, De Vera A, Cremer M, et al. Long-term (>7-year) efficacy and safety data from a phase II extension study of fingolimod in relapsing multiple sclerosis. Journal of Neurology. 2012;259(1 SUPPL. 1):S69–70. Montalban X, Comi G, Antel J, O’Connor P, De Vera A, Cremer M, et al. Long-term (>7-year) efficacy and safety data from a phase II extension study of fingolimod in relapsing multiple sclerosis. Journal of Neurology. 2012;259(1 SUPPL. 1):S69–70.
29.
Zurück zum Zitat Velter C, Thomas M, Cavalcanti A, Bastien M, Chochon F, Lubetzki C, et al. Melanoma during fingolimod treatment for multiple sclerosis. Eur J Cancer. 2019;113:75–7.CrossRefPubMed Velter C, Thomas M, Cavalcanti A, Bastien M, Chochon F, Lubetzki C, et al. Melanoma during fingolimod treatment for multiple sclerosis. Eur J Cancer. 2019;113:75–7.CrossRefPubMed
30.
Zurück zum Zitat Conzett KB, Kolm I, Jelcic I, Kamarachev J, Dummer R, Braun R, et al. Melanoma occurring during treatment with fingolimod for multiple sclerosis: a case report. Arch Dermatol. 2011;147(8):991–2.CrossRefPubMed Conzett KB, Kolm I, Jelcic I, Kamarachev J, Dummer R, Braun R, et al. Melanoma occurring during treatment with fingolimod for multiple sclerosis: a case report. Arch Dermatol. 2011;147(8):991–2.CrossRefPubMed
31.
Zurück zum Zitat Havla JB, Pellkofer HL, Meinl I, Gerdes LA, Hohlfeld R, Kümpfel T. Rebound of disease activity after withdrawal of fingolimod (FTY720) treatment. Arch Neurol. 2012;69(2):262–4.CrossRefPubMed Havla JB, Pellkofer HL, Meinl I, Gerdes LA, Hohlfeld R, Kümpfel T. Rebound of disease activity after withdrawal of fingolimod (FTY720) treatment. Arch Neurol. 2012;69(2):262–4.CrossRefPubMed
32.
Zurück zum Zitat Carbone ML, Lacal PM, Messinese S, De Giglio L, Pozzilli C, Persechino S, et al. Multiple Sclerosis Treatment and Melanoma Development. Int J Mol Sci. 2020;21(8). Carbone ML, Lacal PM, Messinese S, De Giglio L, Pozzilli C, Persechino S, et al. Multiple Sclerosis Treatment and Melanoma Development. Int J Mol Sci. 2020;21(8).
33.
Zurück zum Zitat Michiels Y, Bugnon O, Michiels JF, Mazellier S. Detection of a new melanoma in a patient treated with fingolimod. BMJ Case Rep. 2019;12(4). Michiels Y, Bugnon O, Michiels JF, Mazellier S. Detection of a new melanoma in a patient treated with fingolimod. BMJ Case Rep. 2019;12(4).
35.
Zurück zum Zitat Norgaard M, Veres K, Didden EM, Wormser D, Magyari M. Multiple sclerosis and cancer incidence: A Danish nationwide cohort study. Mult Scler Relat Disord. 2019;28:81–5.CrossRefPubMed Norgaard M, Veres K, Didden EM, Wormser D, Magyari M. Multiple sclerosis and cancer incidence: A Danish nationwide cohort study. Mult Scler Relat Disord. 2019;28:81–5.CrossRefPubMed
36.
Zurück zum Zitat Marrie RA, Reider N, Cohen J, Stuve O, Trojano M, Sorensen PS, et al. A systematic review of the incidence and prevalence of cancer in multiple sclerosis. Multiple Sclerosis Journal. 2015;21(3):294–304.CrossRefPubMed Marrie RA, Reider N, Cohen J, Stuve O, Trojano M, Sorensen PS, et al. A systematic review of the incidence and prevalence of cancer in multiple sclerosis. Multiple Sclerosis Journal. 2015;21(3):294–304.CrossRefPubMed
37.
Zurück zum Zitat Smith KJ, Hamza S, Skelton H. Histologic features in primary cutaneous squamous cell carcinomas in immunocompromised patients focusing on organ transplant patients. Dermatol Surg. 2004;30(4 Pt 2):634–41.PubMed Smith KJ, Hamza S, Skelton H. Histologic features in primary cutaneous squamous cell carcinomas in immunocompromised patients focusing on organ transplant patients. Dermatol Surg. 2004;30(4 Pt 2):634–41.PubMed
38.
Zurück zum Zitat Yamaguchi H, Kitayama J, Takuwa N, Arikawa K, Inoki I, Takehara K, et al. Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. Biochem J. 2003;374(Pt 3):715–22.CrossRefPubMedPubMedCentral Yamaguchi H, Kitayama J, Takuwa N, Arikawa K, Inoki I, Takehara K, et al. Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. Biochem J. 2003;374(Pt 3):715–22.CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. [homepage on the internet] Lyon, France: International Agency for Research on Cancer; 2020 [cited 2022 Jul 20]. Available from: https://gco.iarc.fr/today. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. [homepage on the internet] Lyon, France: International Agency for Research on Cancer; 2020 [cited 2022 Jul 20]. Available from: https://​gco.​iarc.​fr/​today.
40.
Zurück zum Zitat Novartis Pharmaceuticals UK Ltd. Gilenya, INN-fingolimod Summary of Product Characteristics. Access date: 07/01/23. Novartis Pharmaceuticals UK Ltd. Gilenya, INN-fingolimod Summary of Product Characteristics. Access date: 07/01/23.
41.
Zurück zum Zitat Barbieri MA, Sorbara EE, Battaglia A, Cicala G, Rizzo V, Spina E, et al. Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database. Front Pharmacol. 2022;13: 808370.CrossRefPubMedPubMedCentral Barbieri MA, Sorbara EE, Battaglia A, Cicala G, Rizzo V, Spina E, et al. Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database. Front Pharmacol. 2022;13: 808370.CrossRefPubMedPubMedCentral
Metadaten
Titel
Incidence and Characteristics of Melanoma in Multiple Sclerosis Patients Treated With Fingolimod: A Systematic Review
verfasst von
Melinda Jiang
Lydia Lam
YiZhong Zhuang
Rudy Goh
Joshua G. Kovoor
Aashray K. Gupta
William B. Smith
Mark Slee
Stephen Bacchi
Publikationsdatum
30.08.2023
Verlag
Springer US
Erschienen in
Current Dermatology Reports / Ausgabe 4/2023
Elektronische ISSN: 2162-4933
DOI
https://doi.org/10.1007/s13671-023-00400-0

Weitere Artikel der Ausgabe 4/2023

Current Dermatology Reports 4/2023 Zur Ausgabe

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Riesenzellarteriitis: 15% der Patienten sind von okkulter Form betroffen

16.05.2024 Riesenzellarteriitis Nachrichten

In einer retrospektiven Untersuchung haben Forschende aus Belgien und den Niederlanden die okkulte Form der Riesenzellarteriitis genauer unter die Lupe genommen. In puncto Therapie und Rezidivraten stellten sie keinen sehr großen Unterschied zu Erkrankten mit kranialen Symptomen fest.

Betalaktam-Allergie: praxisnahes Vorgehen beim Delabeling

16.05.2024 Pädiatrische Allergologie Nachrichten

Die große Mehrheit der vermeintlichen Penicillinallergien sind keine. Da das „Etikett“ Betalaktam-Allergie oft schon in der Kindheit erworben wird, kann ein frühzeitiges Delabeling lebenslange Vorteile bringen. Ein Team von Pädiaterinnen und Pädiatern aus Kanada stellt vor, wie sie dabei vorgehen.

Isotretinoin: Risiko für schwere Laboranomalien „marginal erhöht“

08.05.2024 Akne Nachrichten

Die Aknetherapie mit Isotretinoin kann einen Anstieg von Leberenzymen und Blutfetten verursachen. Das Risiko für schwere Störungen ist laut einer Forschungsgruppe der Universität Lübeck aber nur marginal erhöht und auf einen engen Zeitraum konzentriert.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.