Event-free survival following treatment with ropeginterferon alfa-2b in patients with PV

Ropeginterferon alfa-2b is a mono-pegylated proline interferon with disease-modifying properties, investigated as part of the PROUD-PV trial (NCT01949805) and its extension trial CONTINUATION-PV (NCT02218047). These trials aimed to establish the efficacy of ropeginterferon alfa-2b in reducing the risk of progression to myelofibrosis (MF) in patients with polycythemia vera (PV).¹

The MPN Hub is pleased to summarize the final 6-year data from PROUD-PV and CONTINUATION-PV, with a focus on event-free survival and safety outcomes.

Study Design¹

The study design and final results of PROUD-PV trial, and interim data from CONTINUATION-PV trial, have been previously published by the MPN Hub.

Briefly, 127 patients from PROUD-PV were treated in each arm, of which 95 patients in the ropeginterferon alfa-2b arm and 74 in the control arm (hydroxyurea [HU] or best available therapy [BAT]) were enrolled into CONTINUATION-PV trial. The baseline characteristics of patients in each arm were comparable.

Following the conclusion of PROUD-PV, patients were assigned an individualized dose-titration of ropeginterferon alfa-2b, with a median cumulative 4-weekly dose of 499 μg. In the control arm, 87.8% of patients remained on HU with a median dose of 1000mg/day. At final data collection, all patients had been treated ≥6 years.

Results¹

Event-free survival and risk

The primary endpoint of this trial was event-free survival (EFS) at 6 years. At data cut off, median EFS had not been reached. The probability of EFS and the number of risk events which occurred in each cohort are outlined in Figures 1 and 2.

EFS, event-free survival; Ropeg alfa-26, ropeginterferon alfa-2b.
*Data from Gisslinger, et al.¹

 

Ropeg alfa-26, ropeginterferon alfa-2b.
*Data from Gisslinger, et al.¹

JAK2^V617F allele burden

A surrogate endpoint of JAK2^V617F allele burden was used as a measure of disease modification. In the ropeginterferon alfa-2b arm, a greater molecular response was observed and a smaller median JAK2^V617F allele burden at 6-years (Figure 3).

Ropeg alfa-26, ropeginterferon alfa-2b.
*Data from Gisslinger, et al.¹

Complete hematologic response

The significantly high complete hematologic response (CHR) at 3-year persisted.

• At 72 months, CHR rate was higher in ropeginterferon alfa-2b compared with control arm (54.5% vs 34.9%, p = 0.02)
• Although the onset of CHR was more gradual in the ropeginterferon alfa-2b arm, the response was more durable compared with control arm (60.9% vs 41.2%, p = 0.04).

Safety¹

Key safety outcomes are summarized in Table 1.

Table 1. Key safety outcomes*

BAT, best available therapy; HU, hydroxyurea; PV, polycythemia vera. *Adapted from Gisslinger, et al.1
Safety outcomes, %	Ropeginterferon alfa-2b (n = 95)	Control (HU or BAT) (n = 74)
Discontinuation of therapy due to drug-related toxicity	11.0	2.4
Grade ≥3 treatment related adverse events	15.7	16.5
PV-associated adverse events	7.1	12.1

Conclusion

Following treatment for ≥6 years, ropeginterferon alfa-2b resulted in an improved EFS compared with HU or BAT. Furthermore, a higher molecular response, accompanied by lower burden of the JAK2^V617F allele was observed with ropeginterferon alfa-2b treatment. However, it is important to note that safety data was not consistently improved compared with the control arm, with a higher number of patients discontinuing treatment and no significant differences observed Grade ≥3 treatment related adverse events.

The long-term results from PROUD-PV and CONTINUATION-PV provide some evidence to support the disease modification properties of ropeginterferon alfa-2b and its application toward reducing the risk of disease progression in patients with PV.