(504) Merkel Cell Carcinoma: A Rare Side Effect of Ruxolitinib Used in Myelofibrosis Treatment

Introduction: MCC is an uncommon form of skin cancer that has been associated with MC Polyomavirus, UV exposure and immunosuppression. Ruxolitinib is an orally administered JAK1/JAK 2 inhibitor 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. Our case reports the association of MCC in a patient receiving long term treatment with Ruxolitinib for Myelofibrosis.

Description: Patient was a 78 year old Polish gentleman with PMH significant for persistent atrial fibrillation, embolic stroke, hypertension and stable AAA. He had multiple admissions for acute on chronic anemia requiring frequent blood transfusions. A bone marrow biopsy showed hypercellular bone marrow and molecular testing revealed mutations in ASXL1, JAK2, and U2AF1, suggesting myelodysplastic syndrome. Initial treatment with Darbepoetin alfa was switched to Ruxolitinib due to inadequate response. After being on ruxolitinib therapy for 4 years, an exophytic mass lesion on the left auricle was noticed. Molecular testing confirmed CD 20, INSM1 positive and TTF-1 negative MCC. Ruxolitinib was discontinued and started on Pacritinib. He was scheduled for outpatient surgical excision of the mass. Prior to the procedure he was admitted to the ED with altered mental status and was found to have S. pyogenes bacteremia due to skin breakdown from earlobe lesion. Despite treatment, his mental status did not improve. After extensive evaluation and in light of his deteriorating condition the decision was made to transition to comfort care.

Discussion: The FDA approved Ruxolitinib for myelofibrosis treatment in 2011 based on the combined findings from the COMFORT-I and COMFORT-II trials. The long-term use has been associated with anemia, opportunistic infections, and a higher incidence of skin cancers. The possible association of Ruxolitinib with MCC could be related to immunosuppression and reactivation of latent MC Polyomavirus . Our case also creates a pertinent link between the use of Ruxolitinib and the development of this aggressive rare neuroendocrine tumor. This warrants the offering of periodic skin examination to patients receiving Ruxolitinib for hematological malignancy.