Year-end Sale % OFF 
Abstract
BackgroundPegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients.MethodsAmong 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6–24 months while on therapy in all patients, and after therapy discontinuation in some patients.ResultsThe median age of analyzed 58 patients was 52 years, and 29% were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69% patients, respectively. Twenty-nine patients (50%) had a BM response, including 13 (22%) with a complete BM response (BM-CR). Moreover, 13 patients (22%) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69%), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous.ConclusionsOur results show the ability of PEG-IFN-α-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation.Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.
Highlights
Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV)
Histomorphology of the bone marrow (BM), including fibrosis grading, and morphological responses according to European LeukemiaNet, International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Consensus [12, 25] were assessed by expert hematopathologists at our institution before study enrollment, every 6–12 months during the first 3 years while on study, and every 12–24 months during the subsequent years
* p value < 0.05 a Significant splenomegaly defined as a palpable spleen > 5 cm below costal margin (BCM), Abnormal karyotype: bone marrow partial response (BM-molecular response (PR)): DER (13;22)(Q10;Q10) (n = 1), + MAR (n = 1), bone marrow complete response (BM-CR): +1, DER (1;22)(Q10;Q10) (n = 1)
Summary
Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Clinical benefit and high HR were noticed in patients with early stages of MF, where interferon-alfa has been shown to possibly reverse bone marrow (BM) fibrosis [9, 10]. We reported a long-term follow-up of a prospective, phase 2 clinical trial of pegylated interferon alfa-2a (PEG-IFN-α-2a) in 83 patients with PV or ET. Despite promising preclinical data showing that the robust immunomodulatory and anti-proliferative effects of interferon-alfa may reverse
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
