Aggressive skin cancers occurring in patients treated with the Janus Kinase inhibitor ruxolitinib

The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution. All patients had a history of myelofibrosis and were exposed to Ruxolitinib. Some patients were exposed to other immunomodulatory medications such as Hydroxyurea and Rituximab. The total number of skin cancers and skin cancers with particularly aggressive behavior were noted. All five patients in this series developed numerous skin cancers with aggressive biological behavior during or after therapy with Ruxolitinib. Also, one patient developed lentigo maligna melanoma and another developed metastatic undifferentiated pleomorphic sarcoma. The repeat observation of skin cancers with aggressive features during JAK inhibitor treatment suggests that these medications may promote cutaneous malignant transformation in at risk patients. Further surveillance and testing of JAK kinases regarding the risk of skin cancers is indicated.