Long-term data of ropeginterferon alpha-2b in polycythaemia vera

Prof. Jean-Jacques Kiladjian (Saint Louis Hospital, France) presented the 4-year follow-up results of the PROUD-PV study its extension study CONTINUATION-PV, which investigated the safety and efficacy of ropeginterferon alpha-2b in patients with polycythaemia vera (PV) [1]. The results were recently published in The Lancet Haematology [2].

Ropeginterferon alpha-2b is a mono-pegylated stabilised form of interferon that requires less frequent dosing. The randomised PROUD-PV trial aimed to demonstrate non-inferiority of ropeginterferon alpha-2b (n=127) when compared with hydroxyurea (n=127) in PV patients. The composite primary endpoint for both studies was complete haematological response (i.e. haematocrit <45% without phlebotomy for at least 3 months, with normal leucocyte and platelet counts) coupled with normal spleen size.

Patients who completed PROUD-PV were allowed to roll-over to CONTINUATION-PV (ropeginterferon alpha-2b continuation arm n=95; the hydroxyurea arm either remained on hydroxyurea or received best-available treatment n=76). At 48-months follow-up, ropeginterferon alpha-2b was superior to hydroxyurea, with 61% of patients in complete haematological remission compared with 43% in the control arm (relative risk 1.43; 95% CI 1.06-1.93; P=0.0194). Clear improvements were also seen in splenomegaly, with 48% of patients on ropeginterferon alpha-2b responding versus 35% in the control arm (relative risk 1.41; 95% CI 0.98-2.01; P=0.0630). At 36 months (CONTINUATION-PV), complete haematological response with improved disease burden was met in 53% of patients in the ropeginterferon alpha-2b group versus 38% of patients in the hydroxyurea group (P=0.044). Removing the spleen criterion further improved the results; complete haematological response was 43% in the ropeginterferon alpha-2b group versus 46% in the standard therapy group at 12 months (PROUD-PV; P=0.63), and 71% versus 51% at 36 months (CONTINUATION-PV; P=0.012).

Notably, during the 4th year of treatment, 42% patients switched from 2-weekly to 4-weekly administration of ropeginterferon alpha-2b. The cumulative dose decreased from about 800 micrograms in Year 1 to just over 500 micrograms in Year 4. Likewise, after 4 years of treatment, 80% of the patients on ropeginterferon alpha-2b were phlebotomy-free as opposed to 60% in the control group (P=0.007; see Figure).

Figure: Phlebotomy-free patients in the PROUD-PV and CONTINUATION-PV trial [1]



After more than 400 patient years in the ropeginterferon alpha-2b arm, there were no differences in major thromboembolic events observed. The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (6%) and alanine aminotransferase (3%) levels in the ropeginterferon alpha-2b group, and leukopenia (5%) and thrombocytopenia (4%) in the standard therapy group. Treatment-related serious adverse events occurred in 2% (3/127) patients in the ropeginterferon alpha-2b group and 4% (5/127) patients in the hydroxyurea group. One treatment-related death due to acute leukaemia occurred in the standard therapy arm.

In summary, these results obtained in a small group of patients suggest that interferon alpha could be a good candidate for restoring normal haematopoiesis in PV patients. Considering the high and durable haematological and molecular responses and a robust tolerability profile, ropeginterferon alpha-2b offers a valuable and safe long-term treatment option.

1. Kiladjian JJ, et al. Abstract 553, ASH 2019, 7-10 December, Orlando, USA.
2. Gisslinger H, et al. The Lancet Haematol. 2020; 7(3): PE196-E208. [Epub ahead of print].

Posted on 5 March 202015 February 2024