Dose Of Interferon Alpha-2a Research Articles

Combination Therapy with Ruxolitinib and Interferon in Newly Diagnosed Patients with Polycythemia Vera

Background: In the COMBI-I trial, we have shown that the combination treatment of Interferon-alpha-2a (IFN) and ruxolitinib is safe and efficacious in patients with polycythemia vera (PV) and myelofibrosis, who were mostly intolerant or refractory to IFN monotherapy. Interferon-alpha2 (IFN) has been used successfully for decades in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. However, 20-30% of patients are intolerant or show limited response to IFN treatment. Ruxolitinib is an anti-inflammatory agent and is used as first-line treatment in patients with myelofibrosis as well as second-line treatment in patients with PV. Combination therapy with the two agents may be more efficacious than monotherapy. Several reports suggest that after achieving a deep hematological and molecular response, treatment pause for several months to years is safe after IFN treatment. Therefore, an initial high-intensity regimen may help to control the disease allowing for treatment pause or low-dose IFN monotherapy. Herein, we report preliminary safety and efficacy data from the COMBI-II trial in patients with newly diagnosed PV. Aims: To evaluate the safety and efficacy of combination therapy with IFN and ruxolitinib in newly diagnosed patients with PV. Methods: A preplanned interim analysis after at least one year of treatment. Twenty-five patients with newly diagnosed PV were included. They were pretreated according to normal clinical standard with phlebotomies and, if high risk, hydroxyurea before inclusion and initiation of combination treatment. Hydroxyurea was withheld 1 week before initiation of treatment. Patients with severe kidney-, liver-, or heart disease were excluded. Initial therapy was IFN (Pegasys®) 45 μg sc/week and ruxolitinib (Jakavi®) 10 mg BID. The study duration was planned to be two years. Safety was assessed by registering all adverse events graded according to the CTCAE V 5.0. Efficacy was evaluated using the 2013 ELN and IWG-MRT response criteria. The JAK2V617F allele burden was measured using high-sensitivity real-time qPCR on whole blood with a lower detection limit of below 0.1%. Histological response, QoL data, and bone marrow MRI results will be presented in the final report. Results: Twenty-five patients with PV were included in 2019-2021. They had a median age of 70 years; 14 were females and 11 were males. Of the 25 patients, 19 patients were high-risk and 6 were low-risk; 5 patients had previous thrombosis. The median time from accepted referral to initiation of treatment was 67 days. The median follow-up time was 21 months. At time of data evaluation, 13 patients had completed 24 months, while 24 patients had completed 12 months of treatment. One patient was withdrawn from the study early due to the development of myelofibrosis 10 months after beginning treatment. One patient was diagnosed with follicular lymphoma 9 months after initiation of treatment. One patient had an acute myocardial infarction. No other thromboembolic events occurred. No grade 3-4 infections were observed. At follow-up, 19 patients were still receiving combination therapy. One patient was receiving concomitant hydroxyurea; 1 ruxolitinib monotherapy; 1 IFN monotherapy; 1 combination of hydroxyurea and IFN; and 1 hydroxyurea monotherapy. Grade 1-2 anemia was frequent and managed with dose reductions. The median doses of ruxolitinib and IFN at follow-up were 5 mg BID and 45 μg sc/2.week, respectively. High rates of complete hematological response were observed after 1 month of treatment (Figure 1). Three patients required phlebotomy after the first 2 weeks of treatment. The JAK2V617F allele burden was significantly reduced 3 months after the start of treatment, and continued to decline from a median of 47% (95%CI 35-59) at baseline to 6% (95%CI 3-12) after 24 months (figure 2);4 patients had a JAK2V617F allele burden < 1%, and 7 patients had a JAK2V617F allele burden below 5% at the latest measurement. No significant difference in JAK2V617F allele burden was observed between referral and initiation of the combination treatment. Conclusion: Combination therapy with IFN and ruxolitinib is relatively well tolerated and is highly efficacious in newly diagnosed PV patients with frequent normalization of cell counts and a marked reduction of the JAK2V617F allele burden. This therapy could lead to a subsequent long-term approach with low-dose interferon or treatment pauses. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Short‐ and long‐term effects of therapy with interferon‐α and pegylated interferon‐α/ribavirin on platelet plug formation and von Willebrand factor release in patients with chronic hepatitis C

A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy. To evaluate the effect of pegylated interferon-alpha administration on platelet plug formation and von Willebrand factor antigen release in patients with chronic hepatitis C. Thirty patients with chronic hepatitis C (genotype 1; fibrosis 1-3: n = 16, cirrhosis: n = 14) received a single dose of 9 MU interferon-alpha2a, followed by weekly administration of 180 mug of pegylated interferon-alpha2a/ribavirin for 48 weeks. Platelet counts, platelet function (collagen-epinephrine-induced closure time) and von Willebrand factor antigen were measured. Platelet counts and collagen-epinephrine-induced closure time decreased by 13% and 16%, respectively, 24 h after the first dose of interferon-alpha2a, and von Willebrand factor antigen levels increased by 31% (P < 0.01) compared with baseline. During a 48-week observation period, platelet counts decreased by a maximum of 33% (P < 0.001), von Willebrand factor antigen levels increased by 69% (P < 0.001) whereas collagen-epinephrine-induced closure time did not change. In noncirrhotic patients, the increase of von Willebrand factor antigen levels was maintained throughout therapy without a change in collagen-epinephrine-induced closure time. In contrast, in cirrhotics, von Willebrand factor antigen levels did not increase, while collagen-epinephrine-induced closure time was prolonged. Single-dose interferon-alpha decreases platelet counts but improves platelet function, possibly by the release of von Willebrand factor antigen. Accordingly, long-term antiviral treatment had no effect on collagen-epinephrine-induced closure time, despite the decrease in platelet count in noncirrhotic patients. Such a compensation of decreased platelet counts by increased von Willebrand factor antigen level did not occur in cirrhotics.

Treatment with Interferon-Alpha2a Alone or Interferon-Alpha2a plus Ribavirin in Patients with Chronic Hepatitis C Previously Treated with Interferon-Alpha2a

Background: Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-reponders or relapsers after IFN treatment. Methods: In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%). Results: Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022). Conclusions: In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-1 patients (11%). Previous IFN responders with relapse responded better than previous non-responders.

Recombinant interferon-alpha combined with prednisone in metastatic renal cell carcinoma reduced toxicity without reduction of the response rate—a phase II study

Five responses (lung metastases, three; lymph node metastases, two) were observed in 23 patients with metastatic renal cell carcinoma who received recombinant interferon-alpha-2A (IFN) 18 X 10(6) U in three intramuscular doses each week combined with oral prednisone (10 to 20 mg daily). The response duration was 4+, 4+, 9, 11+, and 15+ months. In general, the combination treatment of interferon and prednisone lead to a significant reduction of the subjective side effects (flu-like symptoms) as compared to a previous experience in patients treated with interferon only. Reduction of the interferon dose or discontinuation of IFN treatment was necessary in only two of 23 patients receiving IFN plus prednisone. Prednisone, however, had little effect on the hepatic toxicity often associated with high-dose IFN treatment. The subjective tolerability of a high dose of IFN is significantly increased if oral prednisone (10-20 mg) is given concomitantly in patients with metastatic renal cell carcinoma without reducing the response rate. Randomized trials will be necessary to confirm the efficacy of the IFN and prednisone combination. In addition, higher doses of IFN combined with prednisone should be evaluated in this malignancy.

Recombinant Leukocyte Interferon Alpha-2A and Medroxyprogesterone in Advanced Renal Cell Carcinoma: A Randomized Trial

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.

Treatment of cutaneous T cell lymphoma with intermediate doses of interferon alpha 2a.

In this study we treated 6 patients with epidermotropic cutaneous T cell lymphoma (CTCL) with intermediate doses of recombinant alpha 2a interferon (18-100 x 10(6) IU/week) for 2-6 months. One patient experienced complete clinical remission in spite of a persistent dense lymphocytic skin infiltrate. One patient was markedly improved and 2 patients were moderately improved. The clinical condition of the 2 remaining patients was unchanged by interferon treatment. In all cases lesions relapsed a few weeks after treatment was discontinued. This study shows that interferon can be used to treat epidermotropic CTCL. However, a 2- to 6-month treatment using moderate doses did not lead to the high percentage of remission previously reported by others with high doses of recombinant alpha 2a interferon, for longer periods. This result suggests that interferon should be used at high doses and/or for long time periods for clinical improvement of CTCL patients.