Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations

Abstract

Key Points Pegylated IFNα induces hematologic and molecular remission in CALR-mutated ET patients. The analysis of additional mutations highlights the presence of subclones with variable evolutions during IFNα therapy.

How I treat essential thrombocythemia

“…On the contrary, pegylated interferon a-2a has been shown to induce sustained complete molecular response in a subset of patients with JAK2 (V617F)-mutant ET. 53,54 In addition, recent reports describe the positive effect of interferon a in patients with CALR-mutant ET 16,55 : this treatment was found to produce high rates of hematologic and molecular responses that in some cases could be maintained after discontinuation of the drug. 55 Although these observations do not necessarily mean that interferon a can modify the natural history of disease, they at least indicate that this drug can target the myeloproliferative clone.…”

“…1,2 In the last few years, there have been significant advances in our understanding of the genetic basis, pathophysiology, and clinical course of ET. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Our article aims to offer up-to-date information and guidance regarding diagnosis and treatment of ET patients. To provide directions in the therapeutic management of common or complex clinical situations of the disease,…”

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018

“…Interferon alfa-2b has been shown to be effective for patients with JAK2-mutated and CALRmutated ET. 27,37 In a randomized, prospective, observational study that included 123 patients with ET, the 5-year PFS rate was 75.9% for those with JAK2-mutated ET compared with 47.6% for those without JAK2 mutation (P<.05). 27 In another study of 31 patients, interferon alfa induced high rates of hematologic and molecular responses in CALRmutated ET.…”

“…Hydroxyurea, [33][34][35] interferon alfa, 25,27,36,37 and peginterferon alfa, 28,30,38 and possibly anagrelide, 34,35 have been shown to be effective for the prevention NCCN Guidelines Insights of venous thrombotic complications in patients with high-risk ET. In a randomized study of 809 patients with highrisk ET, hydroxyurea plus low-dose aspirin was superior to anagrelide plus low-dose aspirin.…”

Long-acting interferon for myeloproliferative neoplasms - an update

“…Molecular CR (defined as undetectable JAK2V617F) achieved in seven patients and lasting from 6 to 18 months, persisted after peg-IFN-α-2a discontinuation in five, suggesting that peg-IFN-α-2a could even eliminate the JAK2-mutated clone. However, relying on JAK2-mutated burden is controversial, given that agreement between hematologic response and molecular response can be poor as shown by Kuriakose et [14,15].…”