Superficial spreading malignant melanoma in a patient on fingolimod therapy for multiple sclerosis

Haebich, Geraldine; Mughal, A. A.; Tofazzal, N

doi:10.1111/ced.12770

Cited by 15 publications

(12 citation statements)

References 3 publications

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“…One case of melanoma was diagnosed 57 months after starting fingolimod 1.25 mg daily and with Breslow depth of 0.9 mm8 while the other case occurred just 2 months into fingolimod 0.5 mg daily with a Breslow depth of 1.5 9. Considering all three cases reports, the combined melanoma events were calculated to occur at 0.3 events per patient-year discussed which can be sparingly compared with the melanoma incidence in patients with multiple sclerosis of 0.22% per year found in a 2015 meta-analysis 10.…”

Section: Discussionmentioning

confidence: 99%

Fingolimod (Gilenya) and melanoma

Robinson

Guo²

2016

BMJ Case Reports

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The Food and Drug Administration (FDA) had approved fingolimod usage for multiple sclerosis in 2010. Melanoma after the usage of fingolimod immunomodulation was reported rarely in clinical trials, and only two case reports exist in the published literature, both occurring in Europe. Most of the incidences reported in clinical trials were in-situ, whereas both case reports were of malignant melanoma. Fingolimod has been found to inhibit metastatic melanoma growth in a mouse model that depends on vascular endothelial growth factor (VEGF)-induced angiogenesis for metastasis. However, there are numerous pathways of angiogenesis and tumour growth found in vivo by which melanoma can expand that do not mandate VEGF. We report a case of superficial spreading malignant melanoma occurring after fingolimod therapy in the USA.

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Section: Discussionmentioning

confidence: 99%

Fingolimod (Gilenya) and melanoma

Robinson

Guo²

2016

BMJ Case Reports

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“…Recently, several cases of malignant melanoma have been documented in patients with multiple sclerosis who were being treated with FTY720 (44)(45)(46), and a relationship between treatment by FTY720 and occurrence of melanoma has been suggested. However, since the exact mechanism of the relationship has not been elucidated, we believe that further studies are necessary.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of vemurafenib and fingolimod (FTY720) in vemurafenib‑resistant melanoma cell lines

et al. 2018

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Vemurafenib, a selective inhibitor of mutated BRAF, is used to treat late-stage melanoma. However, resistance to vemurafenib is urgently required as it can have fatal consequences. Fingolimod (FTY720), a sphingosine-1-phosphate receptor modulator, has been used for the treatment of several malignant neoplasms in clinical trials. The present study investigated the effects of FTY720 and vemurafenib combination treatment on cell death induction, and defined the molecular mechanisms in vemurafenib-resistant melanoma cells. The combination treatment with FTY720 and vemurafenib reduced cell viability, and the expression of apoptosis-associated cleaved poly (adenosine diphosphate-ribose) polymerase (PARP) was increased when compared with treatment with vemurafenib alone in WM-115 cells, a vemurafenib-resistant human melanoma cell line. In addition, the protein expression of phosphorylated extracellular signal-related kinase (ERK) in WM-115 cells was decreased by this combination treatment. Vemurafenib-resistant SK-Mel-28 cells (R-SK-Mel) were established by culturing SK-Mel-28 cells, which are the most sensitive to vemurafenib, in the presence of vemurafenib. Similar to WM-155 cells, the viability of R-SK-Mel cells was reduced and the expression of cleaved PARP was increased by the combination treatment with FTY720 and vemurafenib. In addition, the expression of phosphorylated ERK and Akt was also reduced by this treatment. These results suggested that FTY720 and vemurafenib synergistically induced cell death by downregulating proliferation and survival signalling pathways in vemurafenib-resistant melanoma cells.

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“…We are convinced that cases of MM arising in patients in treatment with fingolimod are currently anecdotal, and no significant evidence of an increased risk of MM exists. In particular, in the case described by Haebich et al ., it is unclear whether a complete clinical and dermoscopic examination had been performed by a specialist prior to fingolimod commencement. The lesion that turned out to be a melanoma might have been overlooked or only superficially assessed in primary care.…”

Section: Characteristics Of the Study Population (N = 488)mentioning

confidence: 97%

“…We read with interest the report by Haebich et al . describing a case of a superficial spreading malignant melanoma (MM) arising 2 months after commencement of fingolimod therapy for multiple sclerosis.…”

Section: Characteristics Of the Study Population (N = 488)mentioning

confidence: 99%