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Ruxolitinib and interferon-a for PV and MF
toxicities of either ruxolitinib or PEG-IFNa2. The drug doses and adverse events over time are shown in Figure 4. The highest number of adverse events was observed with- in the first 3 months of treatment.
Subgroup analyses
Of 32 PV patients who initiated treatment, 20 complet- ed the study per protocol. Of these 20 patients, ten (50%) achieved remission; three (15%) had CR, and seven (35%) had PR. Eight of the 20 patients (40%) had a MR. At 2 years, 16 (80%) were in PBCR. Of the 18 MF patients who initiated treatment, 12 completed the study per protocol. Of these 12 patients, eight (67%) achieved remission; five (42%) had CR, three (25%) had PR. Two (13%) had a clin- ical improvement. Six patients (50%) had a MR, and nine (75%) were in PBCR.
Eight patients with the JAK2 V617F mutation discontin- ued PEG-IFNa2 and continued ruxolitinib as monothera- py. Their JAK2 V617F allele burdens are shown in Online Supplementary Figure S7. Of these patients, three had PBCR, and none had remission at 24 months. Three achieved MR; however, two of these continued PEG- IFNa2 until 15 and 21 months.
We stratified the main results based on the reason for the prior discontinuation of PEG-IFNa2 (Online Supplementary Table S3). Patients who were previously intolerant of PEG-IFNa2 or naïve to this treatment had more substantial reductions in the JAK2 V617F allele bur- den compared with patients previously refractory to PEG- IFNa2 treatment (mean reductions 61%, 65%, and 34%, respectively). None of the three PEG-IFNa2-naïve patients dropped out or discontinued PEG-IFNa2 treatment, and two achieved remission and MR. We observed no other notable differences.
Discussion
In this study, we showed that a novel combination of ruxolitinib and low-dose PEG-IFNa2 is an effective treat- ment with acceptable toxicity for patients with PV or MF. We observed remission rates of 31% for patients with PV and 44% for patients with MF. Moreover, both groups had relatively high rates of sustained PBCR. Furthermore, we found statistically significant reductions in the MPN-SAF TSS, spleen size, and JAK2 V617F allele burden. The drop-
Figure 4. Adverse events and drug doses in patients with polycythemia vera (left) and myelofibrosis (right). The number of adverse events per patient during the study period with mean doses of pegylated interferon- a2 (PEG-IFNa2) and ruxolitinib (RUX). Gr. 1-2 non-hem AEs: grade 1- 2 non-hematologic adverse events; gr. 3-4 non-hem AEs: grade 3-4 non- hematologic adverse events; All gr. hem AEs: All grade hematologic adverse events.
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