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Increased Risk of Keratinocyte Carcinomas, Merkel Cell Carcinoma, and Other Skin Cancers in Patients Treated With Janus Kinase 1 and 2 Inhibitor, Ruxolitinib
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Non-melanoma skin cancers in ruxolitinib-treated MPN patients behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis . Vigilant skin assessment, counselling on NMSC risks, and prospective ruxolitinib-NMSC studies are crucial.
Background:
Clinical trials report occurrence of non-melanoma skin cancers (NMSC) with ruxolitinib in polycythemia (PV) or myelofibrosis (MF) patients, however the level of risk and effect of covariates are not known in the real-world setting.
Objective:
To systematically assess the risk of developing non-melanoma skin cancer (NMSC) after ruxolitinib exposure in PV or MF patients.
Methods:
A 10-year retrospective cohort of PV or MF patients at Stanford Medical Center was identified and matched on age, gender, race, Charlson comorbidity index, disease diagnosis, and follow-up time. The main outcome measure was Hazard Ratio (HR) for NMSC (comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) after ruxolitinib exposure, adjusted for covariates.
Results:
The study cohort consisted of 564 patients (188 exposed to ruxolitinib for at least 4 weeks, 376 unexposed). Ruxolitinib-exposed PV or MF patients had an adjusted NMSC HR of 2.69 (95% Confidence Interval (CI), 1.03-7.02). In particular, ruxolitinib exposure was associated with SCC, HR=3.24 (95% CI, 1.45-7.22), with non-JAK2 mutated patients showing even higher SCC risk, HR=7.40 (2.54-21.63).
Limitations:
Retrospective design.
Conclusions and relevance:
Our real-world results indicate that SCC risk is increased in PV or MF patients taking ruxolitinib and supports consideration of skin cancer monitoring.
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. It is highly aggressive and represents the second most common cause of skin cancer-related death. Ruxolitinib is an orally administered selective inhibitor of Janus associated kinases1 and 2, which is used in the management of patients with symptomatic myelofibrosis and polycythemia vera who are non-responders or intolerant to hydroxyurea. Herein, we report the case of a 47-year-old woman with a 14-year history of chronic myeloproliferative syndrome initially treated with hydroxyurea for 4 years. She was then enrolled in the Response trial and treated for 7 years with ruxolitinib subsequently developing an MCC. This report shows the possibility of development of MCC in patients treated with ruxolitinib. Periodic skin examination is indicated in patients who undergo ruxolitinib therapy, especially if they have a history of skin cancer; dermatologists and oncohematologists should be aware of this possibility in order to introduce appropriate preventive strategies.