Ropeginterferon alfa-2b is effective and safe in patients older than 60 years with PV

As discussed in our last editorial theme, the pegylated forms of interferon-alpha improve treatment compliance and lower the needed dosing. This leads to a better safety profile, especially for older patients with myeloproliferative neoplasms (MPN).

In January 2020, Heinz Gisslinger and colleagues reported the results of the phase III trial, PROUD-PV, and its extension study, the CONTINUATION-PV trial.¹ Please refer to this previous article on the MPN Hub for a summary of the study design, patient baseline characteristics, and key clinical outcomes. Here, we summarize the recently published subanalysis of the PROUD-PV trial on the use of ropeginterferon alfa-2b (ropeg) versus hydroxyurea (HU) in patients with polycythemia vera (PV) according to their age.²

Subanalysis of ropeginterferon alfa-2b according to age²

Age subanalysis included all patients enrolled in the CONTINUATION-PV study:

• A total of 254 patients were randomized 1:1 to receive ropeg or HU for 1 year in the PROUD-PV trial (NCT01949805). Most were included subsequently in the CONTINUATION-PV extension study (NCT02218047; N = 171) and continued their treatment with ropeg or best available therapy (98.4% of the control arm continued with HU) as long as it was safe and effective (study ongoing).

Overall, the study population was considered young, with a median age of 58 years and 59 years in the ropeg and HU arms, respectively. When grouped into < 60 years and ≥ 60 years, age groups were balanced for the most relevant patient characteristics.

After 24 months from ropeg treatment initiation, patients ≥ 60 years received a median dose of 500 μg every 2–4 weeks, while patients < 60 received a median of 350 μg. In the control arm, both groups received HU at a median dose of 1000 mg/day.

Efficacy

• Ropeg achieved significantly higher rates of complete hematological responses (CHR), maintenance of CHR at 24 months, and molecular responses regardless of age. CHR was defined as reported previously by Quintás-Cardama et al.³
• Patients ≥ 60 years showed a positive trend toward disease-related symptom improvement and reduced JAK2^V617F allele burden, but differences with the control arm were smaller than those seen in the younger subgroup (Figure 1).
• Patients older than 70 years benefited from ropeg treatment similarly to the ≥ 60 years subgroup; however, due to the small sample size interpretation of data is difficult (nine patients treated with ropeg and 12 with HU).

Safety

• The adverse event (AE) incidence of any grade was comparable between treatment arms and age subgroups. However, patients ≥ 60 years experienced more serious AEs than younger patients, leading to a higher AE-related discontinuation rate (in the ropeg arm, ≥ 60 years: 6.5%; < 60 years: 0%).
• By contrast, when analyzing AEs associated with treatment, patients ≥ 60 years treated with ropeg experienced fewer AEs (63%) compared to those treated with HU (89.2%) and even compared to younger patients (ropeg, 77.6%; HU, 74.4%)(Figure 1).