Individualized Dosing of Ropeginterferon Alfa-2b Ensures Optimal Response in Patients with Low-Risk Polycythemia Vera (PV)

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4563-4563
• Main Authors: Gisslinger, Heinz, Klade, Christoph, Georgiev, Pencho, Krochmalczyk, Dorota, Gercheva-Kyuchukova, Liana, Egyed, Miklos, Dulicek, Petr, Illes, Arpad, Pylypenko, Halyna, Sivcheva, Liliya, Mayer, Jiri, Yablokova, Vera, Krejcy, Kurt, Empson, Victoria, Hasselbalch, Hans, Kralovics, Robert, Kiladjian, Jean-Jacques
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-173499

Introduction: Ropeginterferon alfa-2b at a fixed dose of 100 µg/2 weeks was efficacious in patients with low-risk polycythemia vera (PV) in the Low-PV trial, but the response rate was lower in a group of patients who switched to ropeginterferon alfa-2b after failing to respond to phlebotomy alone (Barbui et al., 2023). The finding that this group had a higher proportion of males and higher baseline values for body-mass index, phlebotomy demand, blood counts and JAK2V617F allele burden suggests that these characteristics might predict a higher dose requirement of ropeginterferon alfa-2b. We analyzed low-risk PV patients from the PROUD-PV/CONTINUATION-PV (NCT01949805/NCT02218047) cohort to examine the impact of baseline characteristics and individually optimized dose levels of ropeginterferon alfa-2b on response status at 12, 24 and 72 months. Methods: Patients diagnosed with PV (WHO 2008 criteria) were randomized 1:1 and received ropeginterferon alfa-2b or standard care for a total of ≥6 years during the 12-month PROUD-PV study and its extension CONTINUATION-PV. Low-risk patients (aged ≤60 years with no history of thrombosis) allocated to the ropeginterferon alfa-2b arm were analyzed. Ropeginterferon alfa-2b was started at a dose of 100 µg/2 weeks (50 µg if transitioning from hydroxyurea) and escalated by 50 µg/2 weeks until blood counts normalized to a maximum of 500 µg/2 weeks. Grade 2-3 drug-related toxicity mandated dose reduction/interruption. During maintenance treatment the dosing interval could be extended to 3-4 weeks. Complete hematologic response (CHR) defined by modified ELN criteria (without the spleen criterion) and safety data at 12, 24 and 72 months were assessed. Results: In the setting of individualized dosing, 33/56 (58.9%) low-risk PV patients allocated to ropeginterferon alfa-2b in PROUD-PV achieved a CHR at month 12. Response rates increased with longer treatment duration; of the 46 low-risk patients enrolled in CONTINUATION-PV; 80.4% and 73.2% of patients with available data achieved a CHR at months 24 and 72, respectively. Baseline characteristics by response status at month 12 indicated that males were overrepresented among non-responders (15/23 non-responders [65.2%] were male vs 11/33 responders [33.3%] [p=0.0291]), and baseline median JAK2V617F allele burden was non-significantly higher in non-responders at 12 months (45.6% vs 35.5%: p=0.1860). However, no significant differences in these baseline parameters were observed by long