Interferon Improves Myelofibrosis-Free Survival in AYA Patients with ET and PV

While cytoreductive drugs did not reduce thrombosis risk in adolescent and young adult (AYA) patients with essential thrombocythemia (ET) and polycythemia vera (PV), interferon “significantly improved” myelofibrosis-free survival (MFS) compared with other treatments, according to a study published in Leukemia.

The retrospective study explored the long-term complications and impact of cytoreductive drugs on patient outcomes, thrombotic risk, and progression to secondary myelofibrosis (sMF) in 348 patients diagnosed with ET (n=278) or PV (n=70) before the age of 25 years. The primary end points were MFS, thrombosis-free survival (TFS), and overall survival. Secondary end points included identification of risk factors associated with thrombotic events and progression to sMF.

In the ET cohort, 147 (53%) patients had JAK2 mutations, 43 (16%) had CALR mutations, 3 (1%) had MPL mutations, and 85 (30%) were triple negative (TN). All patients with PV had JAK2 mutations.

A total of 237 (68%) patients were treated with a cytoreductive drug, including 185 patients with ET (66.5%) and 52 patients with PV (74.3%). Patients received one line of therapy (n=97; 41%), two lines of therapy (n=82; 35%), or three or more lines of therapy (n=58; 24%). The most prescribed first-line treatments were hydroxycarbamide (n=126; 53%), interferon (n=55; 23%), anagrelide (n=52; 22%), and alternative drugs (n=4; 2%). The median follow-up was 8.5 years.

Thrombotic Risk

Forty-four patients presented 57 thrombotic events, with a risk of 1.9 per 100 patient-years. The 10- and 20-year probability of TFS was 86.8% and 78.8% for the entire cohort, 86.9% and 80.0% for patients with ET, and 84.4% and 76.3% for patients with PV.

In a multivariate analysis, elevated white blood cell count (>11 × 10⁹/L; hazard ratio [HR], 2.7; P=0.012) and the absence of splenomegaly at diagnosis (HR, 5.7; P=0.026) were associated with increased risk for thrombosis.

Choice of first treatment did not correlate with differences in TFS. The 10- and 20-year TFS were 83.9% and 79.9% for interferon, 81.4% and 70.2% for hydroxycarbamide, and 91.6% and 76.3% for anagrelide (P=0.281)

Myelofibrosis Progression

Twenty-two patients experienced progression to MF, including 18 with ET and 4 with PV, with a risk of 0.7 per 100 patient-years. The 10- and 20-year MFS was 95.2% and 81.3% for the entire cohort, 94.7% and 75.7% for patients with ET, and 96.8% and 93.3% for patients with PV. In a multivariate analysis, progression risk was associated with CALR mutations and a history of thrombosis (HR, 3.8; P=0.015).

The 10- and 20-year MFS were both 100% for interferon, 92.7% and 74.1% for hydroxycarbamide, 91.6% and 73.3% for anagrelide, and 94.2% and 74.0% for no cytoreductive drugs. Compared with patients who received one line of treatment, the risk of sMF progression was higher for those who received two lines of any cytoreductive drug.