Elsevier

Leukemia Research

Volume 54, March 2017, Pages 73-77
Leukemia Research

Pegylated interferon alpha – 2a is clinically effective and tolerable in myeloproliferative neoplasm patients treated off clinical trial

https://doi.org/10.1016/j.leukres.2017.01.006Get rights and content

Highlights

  • Peg IFN 2a is active and well-tolerated therapy outside of a clinical trial.

  • In PV and ET patients, a CR or PR was obtained in 78.6% of treated patients.

  • In MF, stable disease was seen in 63.2% of patients.

  • Grade 3 toxicity was uncommon with leukopenia noted in 1 patient (1.3%).

  • Further data is required to establish the role of Peg IFN 2a in MPN therapy.

Abstract

Polycythemia vera, essential thrombocytosis, and myelofibrosis are chronic Philadelphia-negative myeloproliferative neoplasms that are characterized by clonal hematopoiesis, splenomegaly, risk of hemorrhagic and thrombotic sequelae, and profound symptom burden. We review the outcomes of 75 myeloproliferative neoplasm patients treated with pegylated interferon alpha 2a off study at an academic medical center. In the 56 treated polycythemia vera and essential thrombocytosis patients, a complete or partial response was obtained in 78.6% of patients per ELN/IWG-MRT revised criteria, with >80% of polycythemia vera patients becoming phlebotomy independent and 60% of essential thrombocytosis patients having platelet normalization with therapy. In the 19 treated myelofibrosis patients, stable disease was seen in 63.2% of patients. Vascular events occurred in 2/75 (2.6%) of treated patients while on therapy. Grade 3 toxicity was uncommon with leukopenia noted in 1 patient (1.3%). The most common adverse event overall was grade 1 fatigue in 18.7%. This retrospective single center analysis demonstrates pegylated interferon alpha 2a is active and well-tolerated therapy outside the support of a clinical trial. These results substantiate the previously reported efficacy of pegylated interferon alpha 2a in myeloproliferative neoplasms. Further prospective and randomized clinical trial data is required to better delineate pegylated interferon alpha 2a’s use in myeloproliferative disease, with emphasis placed on comprehensive molecular characterization, allelic burden quantification, and measurement of histologic response.

Introduction

Polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) are chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) that are characterized by clonal hematopoiesis, splenomegaly, risk of hemorrhagic and thrombotic sequelae, and profound symptom burdens [1], [2]. The discovery of the JAKV617F somatic mutation and the subsequent constitutively active tyrosine kinase activity has led to a therapeutic revolution in the treatment of MPNs. Ruxolitinib, an orally available JAK inhibitor, has led to reductions in splenomegaly, improved symptom burden, and improvement in overall survival [3], [4], [5], [6]. Despite this, treatment of MPNs continues to be a challenge secondary to dose limiting cytopenias associated with JAK inhibition [7], [8], [9]. Interferon alpha 2a (IFNα2a) has been of clinical interest in MPNs for over two decades and was noted to be an effective agent for cytoreduction [10], [11]. Although early interferon therapy was associated clinical efficacy, it’s significant toxicity profile restricted its clinical utility. Later, the introduction of pegylated interferon α2a (peg IFN α2a) presented a more tolerable and convenient form of interferon therapy and restored interest in its use for the treatment of MPN patients. Peg IFN α2a was subsequently shown in clinical trials to induce clinical, hematologic, molecular, and histologic responses in treated MPN patients [12], [13], [14], [15], [16], [17]. Additionally, the expected enhanced tolerability of pegylated interferon was confirmed in an international multicenter retrospective analysis [18]. Interestingly, Peg IFN α2a has therapeutic effects beyond cytoreduction including decrease in JAKV617F mutational (allelic) burden and reduction in marrow fibrosis indicating that it may targeting the MPN progenitor and stem cells [19], [20], [21], [22]. Momentum for peg IFN α2a therapy in the treatment of MPN patients continues to build with many ongoing clinical trials (clinicaltrials.gov NCT00452034, NCT01259817, NCT02218047, NCT01259856). Here we discuss outcomes of MPN patients treated with peg IFN α2a seen outside of a clinical trial setting at an academic medical center.

Section snippets

Methods

Patients treated with peg IFN α2a outside a clinical trial between the years 2006 and 2015 were identified at Mayo Clinic, Scottsdale. Charts were reviewed retrospectively, using the electronic medical records, for demographic and clinical data. Toxicity to therapy was assessed using the CTCAE 4.0 criteria. Therapeutic responses for ET and PV were calculated by the revised ELN/IWG-MRT criteria including complete remission (CR), partial remission (PR), no response (NR), or progressive disease

Patients

Seventy five MPN patients treated with pegylated interferon outside of a clinical trial setting between the years 2006 and 2015 were identified. There were 36 PV patients (48%), 20 ET patients (26.7%), and 19 MF patients (25.6%). Thirteen MF patients were post-PV/ET MF. The median age at diagnosis was 51.5 yrs (range 28.8–75.1). JAK2 V617 mutation was present in 53 patients (70.7%). PV risk scores [27] (n = 36) include: Low in 10 (27.7%), Intermediate in 18 (50%), High in 7 (19.4%) and unknown in

Discussion

In this single center retrospective analysis we report peg IFN α2a is clinically active and well-tolerated when administered outside of the support of a clinical trial. This analysis substantiates prior reports of effective hematologic cytoreduction and vascular event risk reduction with interferon therapy in MPN patients. It additionally, reinforces the prior reports of tolerability of pegylated interferon alpha 2a. The majority of patients in this analysis had previously failed cytoreductive

Conclusion

Peg IFN α2A is an active and well-tolerated therapy for MPN patients outside the support of a clinical trial. These results substantiate the previously reported efficacy of peg IFN α2a in MPNs. Further prospective and randomized clinical trial data is be required to better delineate its use in the expanding and complex environment of MPN therapy.

Acknowledgement

None.

References (39)

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