Combination therapy with interferon-α2 and ruxolitinib produced remission in 39% of patients with myelofibrosis (MF) and 9% of polycythemia vera (PV) patients, Danish researchers reported in Cancer Medicine.

Ruxolitinib inhibits Janus kinase 2 (JAK2), one of three driver mutations common in Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs), which include myelofibrosis, PV and essential thrombocythemia. Ruxolitinib significantly diminishes inflammation associated with MF and PV, reduces splenomegaly and relieves constitutional symptoms associated with PV and MF. It does not significantly reduce the burden of the malignant JAK mutations in most patients.

Combination therapy. Source: Getty

Interferon-α2 has demonstrated powerful antiproliferative and immunomodulatory effects and can induce remissions that persist for years after treatment. Its toxicity leads to high rates of discontinuation, however, and a substantial percentage of patients fail to respond to the therapy.

The investigators enrolled 51 adult patients with low- or intermediate-risk PV (32) or MF (19) in a phase 2 study that combined ruxolitinib and pegylated interferon-α2 in a treatment regimen with a maximum duration of 24 months. All patients had active disease and received 75 mg of aspirin. Nearly all the patients (94%) were intolerant or refractory to interferon-α2.

Six patients did not have JAK2 mutations. Four of them had CALR mutations and two had none of the three common mutations.

One patient with MF progressed to acute myeloid leukemia and died after receiving the first treatment dose, but before the first assessment at two weeks. The remaining 50 were included in the efficacy analysis.

Three MF patients (17%) achieved complete remission. Four (22%) achieved partial remission. Remission was seen in patients with primary MF, post-PV MF, and post-essential thrombocythemia MF. Six (33%) had stable disease. Six patients had complete hematologic response at baseline, though they still exhibited symptoms, and 11 of the 12 remaining had CHR during the study. Seven of those patients (58%) sustained CHR for at least three months, extending through the 12 month follow up.

In terms of molecular response, 83% of MF patients experienced a decline in the JAK2V617F allele burden and half of these patients had no evidence of a plateau. Median burden dropped from 45% to 18% at 12 months. No patients achieved complete molecular response.

Among the PV patients, three achieved partial remission (9%) and none had complete remission. Five patients were in complete hematologic response at baseline and maintained that through the study. An additional 22 patients had CHR as some point in the study and 12 (44%) patients sustained CHR for at least three months, including through the 12 month assessment.

 JAK2V617F allele burden declined in 88% of PV patients, with half not demonstrating a plateau. Burden dropped from a median of 47% at baseline to 23.5% at 12 months. No patient achieved complete molecular response.

Serious adverse events requiring hospitalization occurred in 23 patients, though the authors noted that many of the hospitalizations were precautionary and most lasted less than 24 hours. To minimize hospitalizations in future studies, they recommended an initial 10 mg BID dose for ruxolitinib instead of the 20 mg BID starting dose used in the study.

At 12 months of follow up, 15 MF patients and 26 PV patients remained on study medication. Six PV and three MF patients discontinued treatment.