Minimal residual disease after long-term interferon-alpha2 treatment: a report on hematological, molecular and histomorphological response patterns in 10 patients with essential thrombocythemia and polycythemia vera

Abstract

Essential thrombocythemia (ET) and polycythemia vera (PV) are Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) characterized by the JAK2 V617F mutation, which can be found in more than 98% of PV patients and in ∼ 50% of ET patients. Assessment of the JAK2 V617F allele burden by a highly sensitive quantitative PCR (qPCR) assay appears to be a useful tool for monitoring minimal residual disease (MRD) and evaluating treatment efficacy. This report expands and substantiates existing data, showing that IFN-alpha2 is a highly potent immunomodulating agent capable of inducing MRD with low-burden JAK2 V617F, major molecular response (MMR), complete hematological remission (CHR) and complete histomorphological normalization of the bone marrow in a sub-set of patients with ET and PV after long-term treatment (≥ 3.5 years). Furthermore, long-lasting hematological, molecular and histomorphological remissions are sustained after discontinuation of IFN-alpha2 for up to ∼ 5-6 years.

Data‐driven analysis of JAK2V617F kinetics during interferon‐alpha2 treatment of patients with polycythemia vera and related neoplasms

“…In recent years, the interest of using IFN in the treatment of MPNs has increased due to studies reporting long‐term treatment with IFN to be associated with MRD in a subset of patients as defined by sustained complete hematological remissions in concert with induction of low‐burden JAK2 V617F and normalization of the bone marrow . Even in the IFN era of 2019 where several safety and efficacy studies have enrolled > 1000 patients during the last 30 years, the MPN scientific community still recommends patients with low risk disease to be observed without any cytoreductive treatment.…”

“…These highly encouraging results have been the focus of increasing interest, since we may enter a new era with “Minimal Residual Disease” (MRD) as a novel treatment goal …”

“…In recent years, the “watch and wait” strategy has been challenged by reports demonstrating the potential of IFN to induce MRD in an increasing number of patients . Furthermore, these studies also indicate that early treatment with IFN increases the chance of sustained hematological and molecular remissions.…”

Recommendations for the use of pegylated interferon‐α in the treatment of classical myeloproliferative neoplasms

“…Similarly, durable complete haematological response (CHR) and a reduction in the mutated CALR allele burden, regardless of the type of CALR mutation, have been noted among ET patients treated with PEG‐IFN . An improvement in bone marrow histopathology after PEG‐IFN therapy has been reported in both PV and ET patients in small studies that have included serial bone marrow evaluations …”

“…Both haematological and molecular responses tend to be durable, and a small percentage of patients maintain CHR after cessation of the drug with follow‐up of at least 2 years . Disappearance of the malignant clone does not mean cure of the MPN, and relapse can rapidly occur after PEG‐IFN discontinuation.…”