Combination of Ruxolitinib and PEG-INF α2 Effectively Treats Patients With Polycythemia Vera, Myelofibrosis

In the first clinical trial of its kind, Danish researchers investigated the efficacy of a combination treatment of ruxolitinib and low-dose pegylated interferon-α2 (PEG-INF α2) in patients with polycythemia vera (PV) and myelofibrosis (MF), according to a study published in Haematologica.

PEG-INF α2 normalizes blood cell counts and may prevent disease-related complications in patients with PV and MF, while ruxolitinib may increase the efficacy and tolerability of PEG-INF α2, according to the authors.

They hypothesized “combination treatment may also have a synergistic effect on the malignant clone, and reduced dosage of both drugs may lead to fewer side effects compared with monotherapies.”

The multicenter, open-label, single arm phase 2 study included 32 patients with PV and took place over 2 years. Ten patients with PV (31%) achieved remission and 3 (9%) achieved complete remission. The trial also included 18 patients with MF; 8 (44%) achieved remission while 5 (28%) achieved complete remission. Forty-six of the patients included were previously intolerant or refractory to PEG-INF α2.

Researchers determined the treatment’s efficacy “based on hematological parameters, quality of life measurements, and Janus kinase-2 (JAK2) V617F allele burden.”

The study yielded the following results:

• Patients with PV had a cumulative incidence of peripheral blood count remission of 0.85
• Patients with MF had a cumulative incidence of peripheral blood count remission of 0.75
• After 2 years, Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total symptom scores decreased from 22 (95% CI, 16-29) at baseline to 15 (95% CI, 10-22)
• Median JAK2 V617F allele burden decreased from 47% (95% CI, 33-61%) to 12% (95% CI, 6-22%)
• 86% of patients previously intolerant to PEG-INF α2 completed the study, and 67% of these received PEG-INF α2 throughout the study

Overall, the “combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with PV or MF,” the researchers said.

In addition, authors observed a statistically significant reduction in MPN-SAF total symptom score (TSS) from baseline to most time points, excluding at 1 and 2 years. Different items of the TSS were significantly reduced “at more than half of the time points, compared with baseline: early satiety (P <.05), night sweats (P <.01), itching (P <.01), and weight loss (P <.001).” There were no significant differences in TSS change between patients with MF and those with PV.

Although the dropout rate of the study was 16%, researchers found it comparable with rates in previous studies of PEG-INF α2.

Reference

Sørensen AL, Mikkelsen SU, Knudsen TA, et al. Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study [published online December 26, 2019]. Haematologica. doi: 10.3324/haematol.2019.235648.