Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival

Abu‐Zeinah, Ghaith; Krichevsky, Spencer; Cruz, Tatiana; Hoberman, Gabriela; Jaber, Diana; Savage, Niamh; Sosner, Claudia; Ritchie, Ellen K.; Scandura, Joseph M.; Silver, Richard T.

doi:10.1038/s41375-021-01183-8

Cited by 70 publications

(69 citation statements)

References 30 publications

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“…A previous retrospective study of PV patients reported that IFN reduced the risk of mortality and transformation into myelofibrosis compared with HU or phlebotomy. 14 The different conclusions that we report might be due to the relatively short follow-up in our study. Finally, there was no significant difference in thrombosis-free survival ( P =0.40), overall survival ( P =0.55), or myelofibrosis-free survival ( P =0.26) between patients who achieved PMR or not.…”

contrasting

confidence: 61%

Conventional interferon-α 2b versus hydroxyurea for newly-diagnosed patients with polycythemia vera in a real world setting: a retrospective study based on 286 patients from a single center

Liu

Zhang

et al. 2022

haematol

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contrasting

confidence: 61%

Conventional interferon-α 2b versus hydroxyurea for newly-diagnosed patients with polycythemia vera in a real world setting: a retrospective study based on 286 patients from a single center

Liu

Zhang

et al. 2022

haematol

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“…The continued controversy over the choice of drug for first line therapy of ET or PV patients at an increased risk for developing thrombotic events 9 is a consequence of the limited numbers of randomized clinical trials performed and the chronic nature of these malignancies limiting the number of thrombotic events that occur during follow-up 5,10 .…”

Section: Discussionmentioning

confidence: 99%

“…Alleviation of symptoms was the criterion least frequently met for achieving a CR and when not requiring symptom resolution, there were no notable differences between CR rates by treatment arm. In PV patients, 41/87 (HU: 21, PEG: 20, 47%) were receiving phlebotomy during the prior 6 months before enrollment with a median number of phlebotomies of 3.0 [1][2][3][4][5][6][7][8][9][10][11][12] for HU and 4.0 [1][2][3][4][5][6][7][8][9][10][11][12][13] for PEG. 33 PV patients (HU: 15, PEG: 18) received phlebotomy during the first year with a median number of phlebotomies of 2.0 [1][2][3][4][5] for HU and 3.0 [1][2][3][4][5][6] for PEG.…”

Section: Responses Clinicohematologic Responsementioning

confidence: 99%

A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia

Mascarenhas

Kosiorek

Prchal

et al. 2022

Blood

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The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856)

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“…In this perspective, neither the "watch and wait strategy" in low-risk ET and PV patients nor treatment with HU seem rational. Instead, treatment with IFN might be highly relevant since it both normalizes elevated cell counts and importantly induces sustained normal cell counts, [47][48][49][50][51][52][53][54][55][56][57][58] which may even be maintained months and even years after the discontinuation of long-term treatment (>5 years) in some patients. 49 This is in sharp contrast to cell count kinetics after discontinuation of HU, which is followed by a recurrence of elevated cell counts after a few days off HU treatment.…”

Section: Discussionmentioning

confidence: 99%

Data‐driven analysis of the kinetics of the JAK2V617F allele burden and blood cell counts during hydroxyurea treatment of patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis

Dam

Pedersen

Knudsen

et al. 2021

European J of Haematology

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Background: Hydroxyurea (HU) treatment of patients with essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) (MPNs) normalizes elevated blood cell counts within weeks in the large majority of patients.Studies on the impact of HU upon the kinetics of the JAK2V617F allele burden, leukocyte, and platelet counts over time are scarce.Purpose: Using data-driven analysis as a novel tool to model the kinetics of the JAK2V617F allele burden and blood cell counts over time during treatment with HU. Material and methods:Using serial measurements of JAK2V617F and correlation analysis of routine hematological values (the Hb-concentration, leukocyte count, platelet count, and lactic dehydrogenase), we present a detailed description and analysis of the kinetics of the JAK2V617F, leukocyte, and platelet counts and lactic dehydrogenase in 27 patients (PV = 18; ET = 7; PMF = 2), who were followed in the Danish randomized trial (DALIAH). To further analyze the JAK2V617F kinetics, we use a machine learning clustering algorithm to group the response patterns.Results: Response patterns were highly heterogeneous, with clustering resulting in 3 groups and 3 outliers. In the large majority of patients, HU treatment was initially associated with a modest decline in the JAK2V617F allele burden in concert with a decline in leukocyte and platelet counts. However, HU did not induce a sustained and continuous decrease in the JAK2V617F allele burden. Conclusion:Using data-driven analysis of the JAK2V617F allele burden, leukocyte, and platelet kinetics during treatment with HU, we have shown that HU does not induce a sustained decrease in the JAK2V617F allele burden and neither induces sustained normalization of elevated cell counts in MPN patients. Our results may explain why MPN patients during treatment with HU still have a substantially increased risk of thrombosis.

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Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival

Cited by 70 publications

References 30 publications

Conventional interferon-α 2b versus hydroxyurea for newly-diagnosed patients with polycythemia vera in a real world setting: a retrospective study based on 286 patients from a single center

Conventional interferon-α 2b versus hydroxyurea for newly-diagnosed patients with polycythemia vera in a real world setting: a retrospective study based on 286 patients from a single center

A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia

Data‐driven analysis of the kinetics of the JAK2V617F allele burden and blood cell counts during hydroxyurea treatment of patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis

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