Treatment outcomes with pegylated interferon in young patients with PV/ET

Myeloproliferative neoplasms (MPN) are very rare in young patients compared with adults. Not surprisingly, diagnostic criteria, risk classification, or treatment guidelines in polycythemia vera (PV) and essential thrombocythemia (ET) focus mainly on adult patients.

Hydroxyurea is commonly used in children for the treatment of PV/ET, however, there are concerns over its impact on leukemic transformation and fertility, and therefore the advice is to use it cautiously. On the other hand, there is years of experience with interferon treatment in adult patients, which is associated with hematologic and molecular responses. With the development of pegylated forms, interferon also shows improved tolerability in adult patients with PV/ET.

Based on a potential benefit of pegylated interferon (Peg) and the lack of knowledge in children with PV/ ET, Nicole Kucine et al. evaluated the outcomes in young patients (aged < 21 years) with PV/ET who received Peg, and the results were recently published in Pediatric Blood & Cancer.¹

Study design

This is a retrospective study, where records were reviewed of patients younger than 21 years who were diagnosed with PV/ET and treated with Peg at any time following diagnosis.

Patients

Characteristics of 13 patients (ET, n = 6; PV, n = 7) are summarized in Table 1. Splenomegaly (n = 6) and splanchnic vein thrombosis (n = 1) were reported at the time of diagnosis.

Table 1. Patient characteristics (N = 13)^*

Treatment with Peg

Of the 13 patients, seven were treated with hydroxyurea before initiating Peg and three patients received hydroxyurea combined with Peg.

Cytoreductive therapy with hydroxyurea was initiated to treat acquired von Willebrand disease, extreme thrombocytosis, severe iron deficiency, and systemic symptoms.

Reasons for initiating Peg treatment were related to concerns for hydroxyurea-associated malignancies, the impact of hydroxyurea on fertility, possible disease-modifying effects of Peg, and side effects related to hydroxyurea.

Results

• Dose levels of Peg varied among patients (range, 45–153 µg) with a median duration of treatment of 24 months (range, 10–168).
• Eight of nine patients with extreme thrombocytosis had reductions in platelet count to below 1000 × 10⁹/L, and platelet count was reduced to < 450 × 10⁹/L in one of these patients.
• There was no improvement in iron deficiency level in two patients with PV and JAK2 exon 12 mutation, despite decreased frequency of phlebotomy.
• JAK2 V617F allele burden was reduced in three patients:

• • From 49% to 32.7% after 3 years in one patient
  • From 53% to 25% after 2 years in one patient
  • From 26% to 21% after 1 year in one patient

• No patients had disease transformation.

Safety

Patient-reported side effects included dizziness, malaise, and injection site reactions not requiring treatment discontinuation. Therefore, treatment continuation rate was high at 62%.

However, five patients discontinued Peg treatment due to:

• Pulmonary embolism after 10.5 years on Peg (n = 1, with PV and JAK2 V617F mutation). Pulmonary embolism and cerebral sinovenous thrombosis after 3 years on Peg (n = 1 with triple-negative PV).

• • Blood counts were normal at the time of thrombosis in both patients

• Depression and anxiety (n = 2).
• Persistent transaminitis after liver transplant (n = 1).

Conclusion

The time of treatment initiation in young patients with PV/ET is still far from clear, and there is a lack of established criteria, such as laboratory values, symptoms, or thrombotic events, to inform the decision-making process. The authors highlight the need for identifying appropriate therapeutic targets in young patients.

In this retrospective case series of 13 pediatric patients, Peg was relatively well tolerated, showed a low discontinuation rate, and was associated with platelet reduction in cases of extreme thrombocytosis. None of the patients experienced transformation of their disease into a fibrotic phase, which has been reported in up to 2% of young patients with PV/ET.

While further evaluation of Peg is deemed necessary in larger trials with young patients, the authors advocate to include interferon as a first-line treatment option in young patients with PV and ET.

Additional content

The World Health Organization (WHO) recently reviewed its diagnostic criteria to include proposed criteria for children with MPN, and Table 2 provides a comparison of diagnostic criteria for adults and pediatric patients.²

Table 2. WHO diagnostic criteria for adult and pediatric patients with polycythemia vera/essential thrombocythemia*