Association Between IPSS Score and JAK Mutation Characterize Patients with Myelofibrosis at High Risk for Thrombosis

Conference Correspondent —December 14, 2021

Primary myelofibrosis (MF), post-essential thrombocytopenia (PET)-MF, and post-polycythemia vera (PPV)-MF are all associated with thrombosis in the arterial and venous vascular beds; however, the frequency at which they occur in these 3 subtypes of patients with MF have not been fully evaluated.

A total of 1010 patients diagnosed with MF (primary MF, 59%; PET-MF, 20%; or PPV-MF, 21%) in 6 European clinics between January 2001 and December 2012 were enrolled in this study. After a median follow-up duration of 3.8 years, 108 thromboses were observed, representing an incidence rate of 2% per patient-year (95% confidence interval [CI], 1.7-2.5). Most of the thromboses were venous (53.7%) versus arterial (46.3%). Venous thrombosis (VT) included deep VT ± pulmonary embolism (23.0%) and splanchnic VT (10.2%). Arterial thromboses were cerebral (stroke, 19.4%), myocardial infarction (12.0%), and peripheral events (8.3%). The highest rate of clot formation was found among patients with PPV-MF (2.79% patients per year), followed by primary MF (1.91%) and PET-MF (1.60%). In the primary MF group, the primary risk factors for developing thrombosis were age, JAK2 mutation, low and intermediate-1 risk score per International Prognostic Scoring System (IPSS). The highest risk for development of thrombosis was associated with both the presence of JAK2 mutation and low or intermediate-1 IPSS risk score (hazard ratio, 1.51; 95% CI, 1.15-1.98; P = .003).

A subset of patients (n = 559) was further categorized and evaluated for development of thrombosis according to therapy type (ie, hydroxyurea [HU], n = 470, or ruxolitinib [RUX], n = 89). The RUX cohort was composed of slightly younger patients with a median age of 63 years compared with 67 years in the HU cohort. The HU group also exhibited fewer symptoms and less spleen enlargement. Median treatment durations were 2.6 years in the HU group and 3 years in the RUX group. The HU group began therapy at the time of diagnosis, whereas patients in the RUX group initiated treatment at a median of 4 years after being diagnosed with MF. From the time of initiation of therapy, a lower rate of thrombosis was observed in the patients treated with RUX compared with treatment with HU (1.28% [95% CI, 0.48-3.41] vs 2.4% [95% CI, 1.78-3.24] per patient-year, respectively).

In MF patients, RUX therapy may provide more protection from thrombotic events compared with HU, but more research is needed to sufficiently evaluate this potential benefit. In addition, factors such as age, JAK mutations, and a low or intermediate IPSS score are highly associated with development of thrombosis in patients with primary MF. Taken together, these findings point to an association between IPSS score and JAK mutation, which may help distinguish MF patients at high risk for thrombosis.

Source: Barbui T, Ghirardi A, Carobbio A, et al. The interaction between IPSS score and JAK2 mutation identifies patients at different vascular risk in primary myelofibrosis. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 236.

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Last modified: December 14, 2021

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