Hydroxyurea Does Not Appear to Increase Second Malignancy Risk in Myeloproliferative Neoplasms

March 28, 2023

Jonathan Goodman, MPhil

Patients with myeloproliferative neoplasms (MPNs) treated with hydroxyurea do not appear to have a higher risk of secondary malignancies (SMs), according to research published in Blood Advances.

Classical Philadelphia chromosome-negative MPNs, which include polycythemia vera (PV), essential thrombocythemia (ET), and primary/secondary myelofibrosis (MF), are linked with an annual risk of transformation into acute myeloid leukemia (AML) of up to 20%.

Previous research has suggested, furthermore, that the use of hydroxyurea — a myelosuppressive agent used as a cytoreductive therapy in the MPN setting — may increase the risk of SMs through interference with DNA synthesis.

For this population-based study, researchers evaluated data from patients with MPNs including PV, ET, and MF to determine whether a link exists between hydroxyurea and SM development, whether hematologic or solid.

Overall, data from 4023 patients with an MPN were included, of whom 2683 had received hydroxyurea. The most common diagnosis was ET (49.1%), while 42% of patients had PV and 8.9% of patients had MF. The median age in the cohort was 77 years, 61.3% of patients were female sex, and 24% of patients had had a previous cancer. All data were obtained from the Surveillance, Epidemiology, and End Results Medicare-linked database.

The median follow-up was 3.25 years. At this point, 489 patients in the overall cohort had developed an SM, which included solid (346 cases), lymphoid (73 cases), and myeloid (70 cases) malignancies.

Analysis showed that, among those treated with hydroxyurea, the cumulative incidence of SM was 19.88%, compared with 22.31% not treated with hydroxyurea (<.01 on a Gray’s test). No differences, furthermore, were noted in the incidence of solid or specific hematologic SMs (=.3) between the 2 groups.

“[Hydroxyurea] use in older patients with MPN was not associated with an increased incidence of SM overall or AML…specifically, supporting [hydroxyurea] as the preferred cytoreductive option for this patient population,” the authors wrote in their report. “However, a longer follow-up may be necessary to confirm these findings.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Wang R, Shallis RM, Stempel JM, et al. Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea. Blood Adv. 2023;7(5):734-743. doi:10.1182/bloodadvances.2022008259

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