Long term molecular responses in a cohort of Danish patients with essential thrombocythemia, polycythemia vera and myelofibrosis treated with recombinant interferon alpha

Larsen, Thomas Stauffer; Iversen, Katrine Fladeland; Hansen, Esben; Mathiasen, Anders Bruun; Marcher, Claus Werenberg; Frederiksen, Mikael; Larsen, Herdis; Helleberg, Inge; Riley, Caroline Hasselbalch; Bjerrum, Ole Weis; Rønnov-Jessen, Dorthe; Møller, Michael; Stricker, Karin de; Vestergaard, Hanne; Hasselbalch, Hans Carl

doi:10.1016/j.leukres.2013.06.012

Cited by 83 publications

(73 citation statements)

References 27 publications

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“…Furthermore, international consensus‐based remission definitions were applied, with remission criteria not only encompassing improvement in or normalization of peripheral blood counts and spleen size, as used in multiple prior studies,9, 10, 13 but also of marrow morphology and disease‐related symptoms. The 2013 revised response criteria were published after the preparation of the study protocol; however, for the evaluation of efficacy in this interim analysis, we chose to adopt these.…”

Section: Discussionmentioning

confidence: 99%

“…Pegylated forms of IFNα2 (PEG‐IFNα2) allow administration once weekly and have proven efficacious in ET9, 10, 11, 12 and PV9, 10, 11, 12, 13, 14, 15. Patients in the early phase of MF, defined by low‐ or intermediate‐risk disease on the Dynamic International Prognostic Scoring System (DIPSS) scale,16 have also been shown to benefit from treatment with IFNα2 9, 17, 18. Of note, in a subset of patients, long‐term treatment with IFNα2 induces deep molecular remission sustained even years after cessation of therapy 9, 10, 11, 13, 14, 15.…”

Section: Introductionmentioning

confidence: 99%

“…Patients in the early phase of MF, defined by low‐ or intermediate‐risk disease on the Dynamic International Prognostic Scoring System (DIPSS) scale,16 have also been shown to benefit from treatment with IFNα2 9, 17, 18. Of note, in a subset of patients, long‐term treatment with IFNα2 induces deep molecular remission sustained even years after cessation of therapy 9, 10, 11, 13, 14, 15. However, the use of IFNα2 is limited by toxicity with an average discontinuation rate of 10‐30% 10, 12, 19.…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis

et al. 2018

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Interferon‐α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation‐mediated toxicity, leading to treatment discontinuation in 10‐30% of patients. Ruxolitinib, a potent anti‐inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon‐α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon‐α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low‐/intermediate‐1‐risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon‐α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow‐up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty‐seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon‐α2 and ruxolitinib is efficacious in patients with low‐/intermediate‐1‐risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis

et al. 2018

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“…14 Preliminary reports document a role for recombinant interferon-α also in early primary and fibrotic-stage myelofibrosis. [15][16][17][18][19] In early primary myelofibrosis, interferon administration is associated with clinical response or disease stability in 480% of patients. Complete resolution of splenomegaly is observed in the majority of cases, while a significant improvement of bone marrow histology (i.e., reduction of bone marrow fibrosis and megakaryocyte atypia) is documented in 26.7% of patients.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 The effects of recombinant interferon-α in myelofibrosis have been less thoroughly investigated. Recent studies suggest an improvement in clinical symptoms and laboratory values in subsets of interferon-treated myelofibrosis patients, [17][18][19] but the effects of this therapy on bone marrow histology have not been reported in detail.…”

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confidence: 99%

Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response

et al. 2015

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Cytokines, Interferons, and Hematopoietic Growth Factors

Epperla¹,

Hanel²,

Talpaz³

2022

Holland‐Frei Cancer Medicine

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Overview Cytokines are a diverse family of signaling molecules encompassing interleukins, interferons, and hematopoietic growth factors. As important mediators of immune responses, cytokines play critical roles and have clinical relevance in cancer. Interleukins have numerous diverse effects in cancer, including influencing the growth, differentiation, or survival of endothelial cells; attracting inflammatory cell types or induce secondary cytokines to regulate angiogenesis; influencing the tumor environment and infiltrating hematopoietic effector cells; inhibiting or stimulating tumor growth; and regulating immune responses. Various immunostimulatory cytokines, including ILs, are administered to patients in an attempt to initiate or augment antitumor immune responses. Interferons are a large family of multifunctional secreted proteins involved in antiviral defense, cell growth regulation, and immune activation. The three types of IFNs, types I, II, and III, signal via specific cell surface receptors and the JAK‐STAT pathway to transcriptionally activate IFN‐regulated genes (IRGs). Alterations in IRG expression result in modulation of receptors for other cytokines, concentration of regulatory proteins on the surface of immune effector cells, and activation of enzymes that control cellular growth and function. Both natural and recombinant IFNs have shown antitumor activity as single agents in more than a dozen malignancies. Hematopoietic growth factors, most notably epoetin, thrombopoietin, and granulocyte colony‐stimulating factor (G‐CSF), are used in the clinic to stimulate the growth and differentiation of red blood cells, platelets, or neutrophils in clinical settings including after chemotherapy or bone marrow transplantation in a restorative role.

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Long term molecular responses in a cohort of Danish patients with essential thrombocythemia, polycythemia vera and myelofibrosis treated with recombinant interferon alpha

Cited by 83 publications

References 27 publications

Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis

Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis

Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response

Cytokines, Interferons, and Hematopoietic Growth Factors

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