Patients with BCL-ABL1-negative myeloproliferative neoplasms (MPNs), which include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), treated with hydroxyurea experienced a substantially higher incidence of skin toxicity compared with those receiving other MPN-related cytoreductive treatments, according to results of a non-interventional study published in Leukemia.

Previously conducted studies have shown an association between treatment with hydroxyurea, the most frequently used long-term cytoreductive therapy for patients with MPNs, and the development of cutaneous adverse events (AEs). Nevertheless, these skin-related AEs may have been underreported due to the retrospective design of these studies.

This observational study enrolled 172 patients with MPNs, including those with PV (35%), ET (35%), and MF (25%), starting in February 2011, and patients were prospectively followed with a data cutoff date in January 2018.

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In the prospective portion of the study, the median treatment and follow-up times were 3.2 years and 4.0 years, respectively, with a total of 213 treatment courses and a treatment course defined as use of 1 cytoreductive therapy for a period of 1 month or longer, administered during this period. 

In addition, the study also included a retrospective portion encompassing the period of time from diagnosis of a MPN until study enrollment for these patients. Median treatment and follow-up times were 3.4 years and 5.5 years, respectively, and 92 treatment courses were delivered during the retrospective study period.

During the overall study period, hydroxyurea was the most frequently used treatment course (49.2%), followed by ruxolitinib (21.6%), anagrelide (16.4%), and interferon alpha (12.8%).

Similar to findings for the overall study period, the majority of prospectively administered treatment courses consisted of hydroxyurea (45.1%), with ruxolitinib (31.0%), anagrelide (12.7%), and interferon alpha (11.3%) administered less frequently.

A key finding of this study was a prospectively assessed hydroxyurea-associated cutaneous AE rate of 55.2%, which included ulcers (15.6%), precancerous lesions (10.4%), skin cancer (4.2%), and various other nonmalignant cutaneous AEs (32.3%).

In contrast, the incidence of cutaneous AEs for those treated with ruxolitinib, anagrelide, and interferon alpha during the prospective portion of the study was 3.0%, 0%, and 12.5%, respectively, with an overall non-hydroxyurea cutaneous AE rate of 4.3%.

Based on these results, the study authors noted that there was “a significant association between [hydroxyurea] treatment and the development of skin toxicity, in particular with regard to ulcerous and (pre-)malignant lesions.”

Of note, while the overall incidence of hydroxyurea-related cutaneous AEs per 100 patient years was found to be 12.5% during the prospective study period, a corresponding assessment of this endpoint for the retrospective study period revealed an overall incidence of only 5.4%.

“An overall [cutaneous AE] incidence twice as high [was observed] when data were evaluated prospectively compared to retrospective analysis, suggesting that [cutaneous AEs] associated with [hydroxyurea] may be underdiagnosed, the study authors concluded.”

Nevertheless,  cutaneous AE survival over time was found to be significantly longer for those receiving non-hydroxyurea-based therapy compared with hydroxyurea in both the prospective (P =.0076) and retrospective (P =.0036) portions of the study.


Stegelmann F, Wille K, Busen H, et al. Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) – on behalf of the German Study Group-MPN [published online July 3, 2020]. Leukemia. doi: 10.1038/s41375-020-0945-3

This article originally appeared on Oncology Nurse Advisor