Treatment of polycythemia vera aims to prevent thromboembolic complications, reduce the risk of progression to acute leukemia or myelofibrosis, and ameliorate the symptom burden; specifically, to improve quality of life, therapy should address the most clinically important symptoms while reducing phlebotomies to avoid iron-deficiency symptoms.
Long-term efficacy and safety of Ropeginterferon alfa-2b ( Besremi ) have been demonstrated in PROUD-PV / CONTINUATION-PV; the final analysis applied a patient-focused approach.
The objective of the study was to analyze the patient-relevant benefit of Ropeginterferon alfa-2b versus Hydroxyurea / best available treatment ( BAT ) over 6 years.
Patients diagnosed with polycythemia vera according to WHO 2008 criteria who were cytoreduction-naïve or Hydroxyurea pre-treated and gave written informed consent were randomized 1:1 to Ropeginterferon alpha-2b or control treatment ( Hydroxyurea ) for one year in PROUD-PV.
In CONTINUATION-PV, control arm patients could switch from Hydroxyurea to BAT therapy.
Patient-reported polycythemia vera symptom burden was assessed based on adverse events documented in the patient diary and recorded at each visit; items defined in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score ( MPN-SAF TSS; fatigue, concentration problems, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers ) and medical synonyms were evaluated post-hoc.
Efficacy assessments included Kaplan-Meier analysis of event-free survival, phlebotomy need and JAK2V617F allele burden.
Analyses were conducted on the CONTINUATION-PV full analysis set over 6 years of treatment.
The full analysis set comprised 95 patients in the Ropeginterferon alfa-2b arm and 74 in the control arm.
Patient-reported symptoms defined in the MPN-SAF TSS were present in a small minority ( 9.5% ) of patients per arm at baseline ( up to week 4 of treatment ) in this early-stage PV population.
Occurrence of the defined symptoms remained low over long-term treatment, reported in 15.7% of patients in the Ropeginterferon alfa-2b arm and 20.7% in the control arm during the 6th year of treatment.
No phlebotomies were required to maintain hematocrit less than 45% in the 6th year of treatment in 81.4% of patients receiving Ropeginterferon alfa-2b compared with 60.0% of patients in the control arm ( p=0.005 ).
Depletion of the JAK2V617F alle burden, which may lower the risk of progression to myelofibrosis, was observed in Ropeginterferon alfa-2b treated patients; JAK2V617F allele burden less than 1% at 6 years was achieved in 19/92 ( 20.7% ) patients in the Ropeginterferon alfa-2b arm with baseline allele burden less than 10%.
One patient met this threshold in the control arm ( 1/70 [ 1.4% ]; p=0.0001 ).
Event-free survival ( risk events: disease progression, death and thromboembolic events ) over 6 years or more of treatment was significantly higher among Ropeginterferon alfa-2b treated patients than the control group ( risk events reported in 5/95 vs 12/74 patients, respectively; p=0.04 [ Log-Rank ] ).
In conclusion, long-term Ropeginterferon alfa-2b therapy fulfils treatment goals important to patients with polycythemia vera: a good quality of life as indicated by a low symptom burden and phlebotomy requirement, the potential to influence myelofibrosis risk, and better event-free survival versus BAT therapy. ( Xagena )
Gisslinger H et al, European Hematology Congress ( EHA ) Hybrid Congress, 2022