Current treatment experiences of ropeginterferon alfa-2b for patients with MPN

Philadelphia-negative myeloproliferative neoplasms (MPN) are a group of heterogeneous disorders characterized by the overproliferation of myeloid lineage cells.¹ The most common types of MPN are polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis (MF), with PV being the most prevalent. Interestingly, >95% of patients diagnosed with PV have the JAK2^V617F mutation. This plays a key role in disease pathogenesis by disrupting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway leading to uncontrolled hematopoietic stem cell proliferation.

Currently, patients who are diagnosed with PV have limited therapeutic options and treatment with interferon therapy remains the only approach to demonstrate induction of both hematologic and molecular remission. In fact, ropeginterferon alfa-2b (ropegIFN alfa-2b) is the only approved pegylated interferon treatment for patients diagnosed with PV without symptomatic splenomegaly in the Czech Republic.¹

In response to this, Podstavková et al.¹ performed a retrospective analysis investigating the latest data around the use of ropegIFN alfa-2b in regular clinical practice compared with outcomes observed in controlled clinical trials. We summarize their findings below.

Study design

This retrospective, non-interventional analysis evaluated patients observed at the Department of Internal Medicine – Hematology and Oncology in Brno between May 2020 and July 2022. Areas of investigation included:

• Therapeutic dosage
• Efficacy
• Safety

All patients were administered treatment every 14 days, with one patient progressing to maintenance therapy during the monitoring period, which entailed reduced treatment once every 4 weeks. The initial doses were as follows:

• 11 patients on 50 µg
• 3 patients on 100 µg

The doses were then increased according to efficacy and tolerance (median, 150 μg; min, 50 μg; max, 250 μg).

Results

A total of 14 patients were included in the analysis, with a median age of 51 years. Most patients had a PV diagnosis, followed by essential thrombocythemia and then secondary MF (Table 1).

Table 1. Patient characteristics*

ET, essential thrombocythemia; MF, secondary myelofibrosis; PV, polycythemia vera. *Adapted from Podstavková, et al.1
Characteristic, n (unless otherwise stated)	All patients (N = 14)
Sex
Male	10
Female	4
Median age, years	51
Diagnosis
PV	11
ET	2
Secondary MF	1
Low thrombotic risk	10
High thrombotic risk	4
Cytoreductive therapy
1 line	0
2 lines	3
≥3 lines	11
Median baseline hematocrit value, %	43.5
Median baseline leukocyte count, × 109/L	6.8
Median baseline thrombocyte count, × 109/L	391

The median time from diagnosis to treatment onset was 21 months, while the median duration of therapy was 266 days. No patient received ropegIFN as a first-line treatment. All patients experienced stabilization and gradual reduction of hematocrit values with ropegIFN alfa-2b treatment. The JAK2^V617F allele burden also decreased over time during the monitored period (Figure 1) and 11 patients experienced a complete hematologic response, with the median time to this response being 5 months.

*Adapted from Podstavková, et al.¹

Throughout the course of the monitoring period, treatment with ropegIFN was discontinued for two patients. The first was diagnosed with PV and had progressed to secondary MF and the other terminated treatment due to health insurance limitations. Adverse events (AEs) were recorded in six patients within the monitoring timeframe (Figure 2).

*Adapted from Podstavková, et al.¹

All AEs observed in this analysis were of low grade according to the Common Terminology Criteria for AEs, with Grade 2 being the highest recorded. There were no flu-like symptoms in any patients and no discontinuation or termination of treatment due to AEs or intolerance. There was one thromboembolic complication that developed during a course of pneumonia brought on by the SARS-CoV-2 virus.

Conclusion

This analysis highlighted a reduction in allele burden and hematocrit value as well as disease stabilization in patients with MPN treated with ropegIFN alfa-2b. Lower doses of ropegIFN alfa-2b were also sufficient to achieve clinical responses in comparison with trial data. In addition to the low frequency of adverse effects, improved tolerability, and good patient compliance, ropegIFN alfa-2b treatment is considered efficacious and safe.