Primary myelofibrosis (MF) is the most aggressive form of bone neoplasms. In patients with essential thrombocytopenia and polycythemia vera, secondary MF (post-essential thrombocytopenia [PET-MF] and post-polycythemia vera [PPV-MF]) often develops due to natural progression of these conditions. Primary MF, PET-MF, and PPV-MF can lead to the formation of both arterial and venous thrombosis. However, the rate at which blood clots form in these settings has not been sufficiently evaluated.
Researchers investigated 1010 patients diagnosed with primary MF (59%), PET-MF (20%), or PPV-MF (21%) in 6 European clinics between January 2001 and December 2012. After a median follow-up period of 3.8 years, 108 thromboses were observed, representing an incidence rate of 2% of patients per year (95% confidence interval [CI], 1.7-2.5). Most of the thromboses were venous (53.7%) compared with arterial (46.3%). Venous thrombosis included deep vein thrombosis ± pulmonary embolism (23.0%) and splanchnic (10.2%). Arterial thromboses were cerebral (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% of 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, and low and intermediate-1 International Prognostic Scoring System (IPSS) score. The highest risk for development of thrombosis was associated with both the presence of JAK2 mutation and low or intermediate-1 IPSS 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, hydroxyurea (HU; n = 470) or ruxolitinib (RUX; n = 89). The RUX group was slightly younger 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 times 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, but 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) versus 2.4% (95% CI, 1.78-3.24) of patients per year, respectively.
In conclusion, IPSS score and JAK mutation status together may be used to identify MF patient subgroups at greatest risk of vascular events such as thrombosis and inform appropriate therapeutic options. The current study demonstrates that age, JAK mutation positivity, and a low or intermediate IPSS score are highly associated with development of thrombosis in patients with primary MF. RUX therapy may provide some protection compared with HU, but more research is needed to sufficiently evaluate this potential benefit.
Source:
Barbui T, Ghirardi A, Caro 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.