PMID- 30701919 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20190403 IS - 0040-3660 (Print) IS - 0040-3660 (Linking) VI - 90 IP - 7 DP - 2018 Aug 17 TI - Cepeginterferon alfa-2b in the treatment of chronic myeloproliferative diseases. PG - 23-29 LID - 10.26442/terarkh201890723-29 [doi] AB - AIM: A comparative evaluation of the effectiveness of different therapeutic strategies in patients with polycythemia vera (PV) and essential thrombocythemia (ET). MATERIALS AND METHODS: Patients with PV or ET, diagnosed according to the criteria WHO 2016 were included in the study. The primary endpoint - 6 months of therapy (clinical-hematological and molecular responses). The secondary endpoint - 12 months of therapy (clinico-hematologic, molecular, histological responses). Sixty three patients were included in the analysis: the first group consisted of 33 patients who received the therapy with ce-pegiterferone alpha-2b (ce-pegalpha-INF-alpha-2b), 10 of them received previous treatment; the second group - 23 patients btained hydroxycarbamide; the third group - 7 patients were treated with recombinant interferon alpha therapy (rINFalpha). In comparison groups, differences in age were revealed: patients receiving hydroxycarbamide therapy were older. Phlebotomy occurred in 36% of patients in the first group, 9% in the second group, and 14% in the third group. RESULTS: By the 6th month of therapy, 43% of the patients receiving the ce-pegalpha-INF-alpha-2b had complete clinical-hematologic response, 36% had partial clinical-hematologic remission and stabilization of the disease was established in 21% cases. No disease progression occured. By the 12th month of therapy, statistically significant differences in terms of efficacy between the different therapeutic groups (p = 0.2462, Fisher's exact test). In all three groups, the allelic load of JAK2V617F decreased: from 50 to 19%, from 22.3 to 15.8%, from 50 to 7.19%, respectively. The lower the allele load positively correlated with better response to therapy, which was observed in all analyzed groups. Hematologic adverse events (AEs) were more frequently observed in patients receiving ce-pegalpha-INF-alpha-2b therapy. Local reactions developed on 3-7 days of therapy as a hyperemic macula at the injection site. Both these reactions and hair loss did not influence on patient's condition. In the second group (patients with hydroxycarbamide therapy) there were changes in the skin and mucous membranes: dry skin, stomatitis, and in older patients new keratomas appeared. The flu-like syndrome was the most common adverse event associated with the therapy of ce-pegalpha-INF-alpha-2b, which fully relived during the first month of therapy. There was only one case with the flu-like syndrome we observed at the 11th month of therapy. As a rule, the biochemical blood test changes did not influence on patient's condition, were mostly associated with dietary violations, had a tendency to self-resolution and did not require medical interventions. Serious AEs were reported in one case - pulmonary embolism in a patient treated with rINFalpha. The reasons for the therapy discontinue in group 1: toxic hepatitis, intolerance, by the request of the patient, inadequate efficacy of therapy; in group 2: skin toxicity, in group 3: thromboses. CONCLUSION: Treatment of ce-pegalpha-INF-alpha-2b in patients with PV and ET is highly effective - the most patients pbtained clinical and hematological responses. There were no statistically significant differences in these parameters in comparison with hydroxycarbamide and rINFalpha. The use of the ce-pegalpha-INF-alpha-2b had an acceptable safety profile. The estimated therapeutic dose should be calculated according to body weight. To reduce the frequency of hematologic AE, titration of the drug dose is required. FAU - Melikyan, A L AU - Melikyan AL AD - National Research Center for hematology, Moscow, Russia. FAU - Subortseva, I N AU - Subortseva IN AD - National Research Center for hematology, Moscow, Russia. FAU - Gilyazitdinova, E A AU - Gilyazitdinova EA AD - National Research Center for hematology, Moscow, Russia. FAU - Koloshejnova, T I AU - Koloshejnova TI AD - National Research Center for hematology, Moscow, Russia. FAU - Pustovaya, E I AU - Pustovaya EI AD - National Research Center for hematology, Moscow, Russia. FAU - Egorova, E K AU - Egorova EK AD - National Research Center for hematology, Moscow, Russia. FAU - Kovrigina, A M AU - Kovrigina AM AD - National Research Center for hematology, Moscow, Russia. FAU - Sudarikov, A B AU - Sudarikov AB AD - National Research Center for hematology, Moscow, Russia. FAU - Abdullaev, A O AU - Abdullaev AO AD - National Research Center for hematology, Moscow, Russia. FAU - Lomaia, E G AU - Lomaia EG AD - Almazov National Medical Research Center, Saint Petersburg, Russia. FAU - Siordiya, N T AU - Siordiya NT AD - Almazov National Medical Research Center, Saint Petersburg, Russia. FAU - Zaritskey, A Yu AU - Zaritskey AY AD - Almazov National Medical Research Center, Saint Petersburg, Russia. FAU - Savchenko, V G AU - Savchenko VG AD - National Research Center for hematology, Moscow, Russia. LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PL - Russia (Federation) TA - Ter Arkh JT - Terapevticheskii arkhiv JID - 2984818R RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (Recombinant Proteins) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Janus Kinase 2) RN - G8RGG88B68 (peginterferon alfa-2b) RN - X6Q56QN5QC (Hydroxyurea) SB - IM MH - Adult MH - Gene Frequency MH - Humans MH - Hydroxyurea/administration & dosage/adverse effects/*therapeutic use MH - Interferon alpha-2/administration & dosage/adverse effects/*therapeutic use MH - Interferon-alpha/administration & dosage/adverse effects/*therapeutic use MH - Janus Kinase 2/genetics MH - Middle Aged MH - Mutation MH - Polycythemia Vera/blood/*drug therapy/genetics MH - Polyethylene Glycols/administration & dosage/adverse effects/*therapeutic use MH - Prospective Studies MH - Recombinant Proteins/administration & dosage/adverse effects/therapeutic use MH - Thrombocythemia, Essential/blood/*drug therapy/genetics MH - Treatment Outcome OTO - NOTNLM OT - JAK2V617F. OT - ce-pegalpha-INF-alpha-2b OT - essential thrombocythemia OT - pegylated interferon alfa-2a / 2b OT - polycythemia vera EDAT- 2019/02/01 06:00 MHDA- 2019/04/04 06:00 CRDT- 2019/02/01 06:00 PHST- 2019/02/01 06:00 [entrez] PHST- 2019/02/01 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] AID - 10.26442/terarkh201890723-29 [doi] PST - ppublish SO - Ter Arkh. 2018 Aug 17;90(7):23-29. doi: 10.26442/terarkh201890723-29.