Ropeginterferon alfa-2b-njft (Besremi) improved complete hematologic response, partial molecular response, and JAK2 V617F allele burden compared with phlebotomy alone in patients with polycythemia vera, according to findings from a systematic review and meta-analysis presented in a poster session at the
In the phase 2 Low-PV trial (NCT03003325), which provided the comparison of ropeginterferon alfa-2b (n = 64) vs phlebotomy (n = 63), 52 of 64 patients treated with ropeginterferon alfa-2b achieved a complete hematologic response (CHR) at 12 months vs 37 of 63 patients in the control arm (odds ratio [OR], 3.05; 95% CI, 1.36-6.80; P = .007). Partial molecular response (PMR) at 12 months occurred in 16 of 55 patients vs 0 of 43 patients, respectively (OR, 36.34; 95% CI, 2.11-625.93; P = .01), and the mean change in JAK2 V617F allele burden favored ropeginterferon alfa-2b (mean difference [MD], −13.70; 95% CI, −19.24 to −8.16; P < .00001).
Against hydroxyurea, which was evaluated in the phase 3 PROUD-PV trial (NCT01949805; ropeginterferon alfa-2b, n = 127; hydroxyurea, n = 127) and its phase 3b extension, CONTINUATION-PV (NCT02218047; ropeginterferon alfa-2b, n = 95; hydroxyurea/best available therapy, n = 76), the pooled ORs were 0.74 (95% CI, 0.46-1.20) for CHR and 0.73 (95% CI, 0.49-1.08) for PMR, and the pooled MD in allele burden was −6.90 (95% CI, −31.59 to 17.80). Across all 3 trials, the overall pooled estimates were 1.11 (95% CI, 0.47-2.63) for CHR, 1.08 (95% CI, 0.40-2.92) for PMR, and −9.13 (95% CI, −29.22 to 10.96) for allele burden.
“Ropeginterferon alfa-2b demonstrates noninferiority to hydroxyurea and superiority over phlebotomy in short-term efficacy for polycythemia vera management,” lead study author Danyal Bakht, MBBS, of King Edward Medical University in Lahore, Pakistan, and colleagues wrote in the poster. “Its favorable molecular and hematologic outcomes support its role as a disease-modifying therapy, particularly in low-risk patients.”
Ropeginterferon alfa-2b, a monopegylated interferon,
The investigators conducted a systematic search of PubMed, Scopus, Cochrane, and Embase through April 2025 in accordance with PRISMA 2020 guidelines, including randomized controlled trials that compared ropeginterferon alfa-2b with standard therapies in patients with polycythemia vera.1 Random-effects models were used to derive ORs for dichotomous outcomes and MDs for continuous outcomes, and sensitivity and subgroup analyses were performed.
Three trials met the inclusion criteria. In Low-PV, ropeginterferon alfa-2b was compared with phlebotomy plus low-dose aspirin; in PROUD-PV, the comparator was hydroxyurea; and in CONTINUATION-PV, the comparator was hydroxyurea or best available therapy.
CHR was defined as hematocrit of 45% or lower maintained without disease progression over 12 months. PMR was defined as a reduction of at least 20% in JAK2 V617F allele frequency from baseline at 12 months per European LeukemiaNet criteria, and the third outcome was the change in mean JAK2 V617F allele burden from baseline. Risk of bias was assessed using the RoB 2.0 tool, with included studies rated as having “some concerns” overall.
Within the hydroxyurea comparison, the OR for CHR was 0.55 (95% CI, 0.28-1.06) in CONTINUATION-PV (59 of 95 vs 57 of 76 patients) and 0.90 (95% CI, 0.55-1.49) in PROUD-PV (53 of 123 vs 57 of 125 patients), with low heterogeneity (I2 = 29%).1 For PMR, the respective ORs were 0.75 (95% CI, 0.41-1.39; 41 of 94 vs 38 of 75 patients) and 0.71 (95% CI, 0.42-1.19; 42 of 123 vs 52 of 123 patients), with no heterogeneity (I2 = 0%).
The allele burden findings diverged between the 2 hydroxyurea-controlled studies: the MD was −19.50 (95% CI, −20.28 to −18.72) in CONTINUATION-PV, favoring ropeginterferon alfa-2b, and 5.70 (95% CI, 5.22-6.18) in PROUD-PV, favoring hydroxyurea (I2 = 100%).
Heterogeneity was substantial for each overall pooled analysis, with I2 values of 81% for CHR, 76% for PMR, and 100% for allele burden.
The phlebotomy comparison rests on a single trial enrolling low-risk patients, and the wide CI around the PMR estimate reflects the absence of molecular responses in the control arm. CONTINUATION-PV enrolled patients who completed PROUD-PV, so the 2 hydroxyurea-controlled datasets are drawn from overlapping patient populations. The outcomes assessed were limited to 12 months, and safety was not reported in the poster.
The authors noted that larger and longer-term trials are needed to confirm these benefits across broader populations.
