Abstract Details

Title No significant risk of malignant melanoma growth under cladribine treatment: in vitro studies

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-018

Objective To explore with in vitro studies if cladribine could be linked to the growth of skin melanoma cells at doses used in multiple sclerosis (MS).

Background

Cladribine is a synthetic purine nucleoside analogue cytotoxic to lymphocytes and, to a lesser degree, monocytes and hematopoietic cells. As a result, cladribine induces a dose-dependent reduction of T and B cells lasting months to years. There is a suspected increase of cancer risk, especially skin cancers, with cladribine. It has been shown that untreated MS patients do not have an increased risk of cancer, including melanoma.

Design/Methods Cell growth assays using a live cell imager were used to determine melanoma viability in response to cladribine. Different nuclear-labeled fluorescent melanoma cells were treated with various concentrations of the drug and cell proliferation was monitored with the IncuCyte ZOOM live cell microscope (Essen BioSciense). Images were taken every 4 hours over a 4-day period. Confluency and number of nuclei (red cell objects) were quantified by IncuCyte software.

Results Cladribine inhibited cell proliferation on three melanoma cell lines tested irrespective of the mutational oncogenic status and their invasive/metastatic potential. Although the three cell lines exhibited slight difference in sensitivity, cladribine was able to inhibit proliferation and survival of all cells in a dose-dependent manner. The IC50 for 501Mel, 1205Lu or m229 cells was approximately 2.9, 2 or 0.5 micromol/L, respectively.

Conclusions

Our study supports that in vitro cladribine displays anti-melanoma activities by itself, suggesting its

therapeutic use in MS does not promote progression of pre-existing melanoma lesions. The suspicion of increased skin cancer risk from cladribine in MS needs to be follow-up in prospective worldwide cohorts.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Christine Lebrun Frenay, MD, FAAN (CRCSEP Neurologie)	Dr. Lebrun Frenay has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Revue Neurologique. The institution of Dr. Lebrun Frenay has received research support from FRANCE SEP.

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