PEG-Intron Therapy in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders (MPD): Final Result of a Phase II Study.
Authors: Jabbour Elias , Kantarjian Hagop , Koller Charles A. , Faderl Stefan , Ferrajoli Alessandra , Richie Mary Ann , Garcia-Manero Guillermo , Cortes Jorge , Estrov Zeev , Ravandi-Kashani Farhad , Giles Francis , Verstovsek Srdan 
Published: October 2019

The conventional management of patients (pts) with high-risk Philadelphia chromosome-negative (Ph-negative) MPD revolves around the administration of cytoreductive agents such as hydroxyurea, anagrelide, and recombinant human interferon alpha (IFN-a). IFN-a has shown significant activity in the treatment of Ph-negative MPD, particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-Intron is a pegylated IFN-a that has a significant advantage over regular IFN-a in that it is administered once a week. We are reporting the final results of a phase II study evaluating the efficacy and tolerability of PEG-Intron in pts with Ph-negative MPD treated at M. D. Anderson Cancer Center, Houston, Texas. PEG-Intron was given subcutaneously weekly with intent to treat pts as long as they benefit from the therapy. Forty pts were enrolled, 26 males (65%), with a median age of 54 years (range 28 to 81). Pts diagnoses were: 14 ET (35%); 11 myelofibrosis (MF; 27%); 6 Ph-negative chronic myeloid leukemia (CML; 15%); 4 hypereosinophilic syndrome (HES; 10%); 4 PV (10%); and 1 myelodysplastic syndrome/myeloproliferative disease (MDS/MPD; 3%). Thirty-four pts are evaluable for response evaluation, as they have received minimum of 3 months of therapy, and have received more than 50% of the medication during the time on study: complete remission (CR) was achieved in 13 pts (38%) while partial response (PR) was noted in 4 pts (12%); 17 pts (50%) had no response. Six pts were not evaluable for response: 2 refused therapy before starting; 3 stopped therapy early due to toxicity, and 1 had progression of the disease before 3 month response evaluation. Of the 17 responders 12 (71%) achieved their best response by 3 months on the therapy. Overall response among all the patients enrolled varied by the type of diagnosis: of the 14 ET pts 7 achieved CR and 2 achieved PR (64% overall response rate); of the 11 MF pts one achieved CR; of the 6 Ph-negative CML 2 achieved CR; of the 4 pts with HES one achieved CR; of 4 PV pts 2 achieved CR and 2 PR; and 1 MDS/MPD pt was not evaluable for response. Initially, starting dose of PEG-Intron was 3 mcg/kg per week. However, of the first 14 pts on the study all but 1 had to reduce the dose at least once within the first 3 months, and therefore the starting dose of PEG-Intron was reduced to 2 mcg/kg per week. Most of the pts maintained the 2 mcg/kg per week throughout their time on the therapy. Recorded grade 3 toxicities were related to myelosuppression, disturbance of GI tract, and musculo-skeletal system (22 pts). Grade 4 toxicities were recorded in 4 pts: 1 developed anemia and the other 3 developed thrombocytopenia. Of the 38 pts that have received any therapy 5 (4 in CR and 1 in PR) are still receiving therapy for a median duration of 28+ months (range, 21+ to 41+). Of the 33 pts that stopped the therapy 17 stopped because of no response, 6 due to unrelated medical reasons, 5 due to toxicity, 2 due to other reasons, 1 was lost to follow-up, 1 lost response, and 1 progressed to acute myeloid leukemia. After a median follow-up of 24 months (range, 1 to 42) 26 pts are alive. In conclusion, PEG-Intron, with proper dose modifications, is effective in controlling disease in a significant proportion of Ph-negative MPD pts, particularly patients with ET and PV. However, toxicities encountered with PEG-Intron therapy are still significant.