Ruxolitinib Found Not to Increase the Risk for Secondary Malignancies in Polycythemia Vera

Treatment with ruxolitinib (Jakafi) was not found to carry an increased risk of secondary malignancies in patients with polycythemia vera, according to findings from a retrospective analysis published in the Annals of Hematology.

The results demonstrated that no significant difference was identified between the number of patients with polycythemia vera with ruxolitinib-associated secondary malignancies (n = 10; 41.7%) and the patients (n = 14; 58.3%) who developed secondary malignancies without ruxolitinib (P = 0.34, chi square test).

“Our data do not show an increased risk of secondary malignancies, particularly lymphoma, in polycythemia vera patients treated with ruxolitinib. Therefore, in high-risk polycythemia vera patients with hydroxyurea intolerance or resistance, concern about developing secondary malignancies does not appear to be a major factor preventing ruxolitinib therapy,” wrote lead study author Rohit Sekhri, of the University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care at Johannes Wesling Medical Center Minden, and coauthors in the study publication.

Ruxolitinib has drawn attention because of its risk for secondary malignancies in patients with myelofibrosis. However, data regarding the risk of secondary malignancies in patients with polycythemia vera treated with the JAK1/2 inhibitor are few and far between.

As such, investigators sought to evaluate the relationship between treatment with ruxolitinib in polycythemia vera and secondary malignancies.

The single-center study comprised 289 patients with JAK2 V617F–mutated polycythemia vera who had been diagnosed according to the World Health Organization 2016 criteria. The enrollment period began on May 14, 2013; data cutoff was December 1, 2020.

Regarding patient demographics, most patients were women (58.8%). At the time of diagnosis, more than half of patients (52.2%) were between 40 and 60 years of age and had low-risk disease (50.5%) according to their polycythemia vera survival score.

Additional results indicated that the median duration of cytoreductive therapy for polycythemia vera was 73.5 months (range, 1.0-311.0).

Most patients received hydroxyurea (n = 185; 64.0%) for a median duration of 45.2 months (range, 0.2-289.0) followed by ruxolitinib, which was given to 32.9% (n = 95/289) of patients for a median duration of 48.0 months (range 1.0-101.6).

At a median follow-up of 97 months (range, 1.0-395.0) following polycythemia vera diagnosis, 24 (8.3%) secondary malignancies were recorded.

The median time to development of the secondary malignancy was 7.2 years (range, 0.1-22.9) after polycythemia vera diagnosis, and the median age at secondary malignancy diagnosis was 69.7 years (range, 29.6-89.5).

Most of the secondary malignancies (n = 9/24; 37.5%) were reported in patients with intermediate-risk disease.

Notably, no increased cases of melanoma (P = .31), lymphoma (P = .60), or solid non-skin malignancies (P = .63, all chi square test) were reported with ruxolitinib.

However, a substantial proportion of non-melanoma skin cancer was seen with ruxolitinib treatment vs without (n = 11; 45.8%; P = .03, chi square test).

The secondary malignancy–free survival was comparable by log rank test for all 289 patients (P = .65), for the patients (n = 208; 72%) receiving cytoreductive therapy (P = .48) or for different treatment sequences (P = .074).

In multivariate analysis, advanced age at polycythemia vera diagnosis (HR, 1.062; 95% CI, 1.028-1.098) but not treatment with ruxolitinib (HR, 1.068; 95% CI, 0.468-2.463) was associated with an increased risk for secondary malignancies (P = .005).

“Our data indicate an increased risk of non-melanoma skin cancer with ruxolitinib therapy, especially in the case of hydroxyurea pretreatment. Therefore, in the future, the evolution of such malignant skin lesions in polycythemia vera patients treated with ruxolitinib should be identified at an early stage by regular dermatological monitoring,” concluded the study authors.

Reference

1. Sekhri R, Sadjadian P, Becker T, et al. Ruxolitinib-treated polycythemia vera patients and their risk of secondary malignancies. Ann Hematol. 2021;100(11):2707-2716. doi:10.1007/s00277-021-04647-0