Long‐term therapeutic efficacy and toxicity of recombinant interferon‐alpha 2a in polycythaemia vera

Foa, P.; Massaro, Paolo; Caldiera, S.; Latargia, Maria Luisa; Iurlo, Alessandra; Clerici, Carlo; Fornier, Monica; Bertoni, Francesco; Maiolo, Anna Teresa

doi:10.1111/j.1600-0609.1998.tb01039.x

Cited by 21 publications

(10 citation statements)

References 12 publications

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“…Recombinant IFNs were shown to improve cancer therapy due to their ability to make the tumors “hot,” i.e., more responsive to immunotherapies . The RNA fibers with controlled immunostimulation may serve as a source of natural IFN response produced by the body's own cells, as opposed to the recombinant IFNs delivered from external sources and associated with systemic toxicity . Moreover, the unique shape of RNA fibers somehow mimics double‐stranded DNA plasmids and therefore the delivery agents that are efficiently used for plasmids in vivo may become suitable for RNA fibers.…”

Section: Resultsmentioning

confidence: 99%

RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition

Rackley

Stewart

Salotti

et al. 2018

Adv Funct Materials

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RNA is a versatile biomaterial that can be used to engineer nanoassemblies for personalized treatment of various diseases. Despite promising advancements, the design of RNA nanoassemblies with minimal recognition by the immune system remains a major challenge. Here, an approach is reported to engineer RNA fibrous structures to operate as a customizable platform for efficient coordination of siRNAs and for maintaining low immunostimulation. Functional RNA fibers are studied in silico and their formation is confirmed by various experimental techniques and visualized by atomic force microscopy (AFM). It is demonstrated that the RNA fibers offer multiple advantages among which are: i) programmability and modular design that allow for simultaneous controlled delivery of multiple siRNAs and fluorophores, ii) reduced immunostimulation when compared to other programmable RNA nanoassemblies, and iii) simple production protocol for endotoxin-free fibers with the option of their cotranscriptional assembly. Furthermore, it is shown that functional RNA fibers can be efficiently delivered with various organic and inorganic carriers while retaining their structural integrity in cells. Specific gene silencing triggered by RNA fibers is assessed in human breast cancer and melanoma cell lines, with the confirmed ability of functional fibers to selectively target single nucleotide mutations.

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Section: Resultsmentioning

confidence: 99%

RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition

Rackley

Stewart

Salotti

et al. 2018

Adv Funct Materials

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“…A similar efficacy has also been observed in terms of reduction of spleen size or relief from pruritus. Interferon-alpha has proved to be a useful treatment option, because, differently from conventional therapeutic approaches, it is devoid of pro-leukemic effect [86][87][88].…”

Section: Interferonmentioning

confidence: 99%

New Perspectives on Polycythemia Vera: From Diagnosis to Therapy

Iurlo

Cattaneo

Bucelli

et al. 2020

IJMS

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Polycythemia vera (PV) is mainly characterized by elevated blood cell counts, thrombotic as well as hemorrhagic predisposition, a variety of symptoms, and cumulative risks of fibrotic progression and/or leukemic evolution over time. Major changes to its diagnostic criteria were made in the 2016 revision of the World Health Organization (WHO) classification, with both hemoglobin and hematocrit diagnostic thresholds lowered to 16.5 g/dL and 49% for men, and 16 g/dL and 48% for women, respectively. The main reason leading to these changes was represented by the recognition of a new entity, namely the so-called “masked PV”, as individuals suffering from this condition have a worse outcome, possibly owing to missed or delayed diagnoses and lower intensity of treatment. Thrombotic risk stratification is of crucial importance to evaluate patients’ prognosis at diagnosis. Currently, patients are stratified into a low-risk group, in the case of younger age (<60 years) and no previous thromboses, and a high-risk group, in the case of patients older than 60 years and/or with a previous thrombotic complication. Furthermore, even though they have not yet been formally included in a scoring system, generic cardiovascular risk factors, particularly hypertension, smoking, and leukocytosis, contribute to the thrombotic overall risk. In the absence of agents proven to modify its natural history and prevent progression, PV management has primarily been focused on minimizing the thrombotic risk, representing the main cause of morbidity and mortality. When cytoreduction is necessary, conventional therapies include hydroxyurea as a first-line treatment and ruxolitinib and interferon in resistant/intolerant cases. Each therapy, however, is burdened by specific drawbacks, underlying the need for improved strategies. Currently, the therapeutic landscape for PV is still expanding, and includes several molecules that are under investigation, like long-acting pegylated interferon alpha-2b, histone deacetylase inhibitors, and murine double minute 2 (MDM2) inhibitors.

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“…Overall, approximately 47%-95% of the patients included in these trials had reduction in the number of phlebotomies, and 6%-85% required no phlebotomies during their treatment period [51]. In one study with longterm follow-up, of the 38 PV patients treated with IFN-a [52] at dose of 9 3 10 6 IU weekly, 11 patients (28.9%) achieved a complete response (maintaining a normal hematocrit without phlebotomy), and 8 patients (21%) achieved partial response (.50% reduction in phlebotomy requirement) [52]. Responses were durable with a 40-month median duration of treatment (range, 12-52 months), but toxicities were observed in 36.7% of the patients requiring treatment discontinuation in all such cases [52].…”

Section: Interferonmentioning

confidence: 99%

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

Nazha

Gerds

2016

The Oncologist

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The goals of therapy in patients with polycythemia vera (PV) are to improve disease‐related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first‐line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6‐fold increase in mortality and a 6.8‐fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon‐α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation. Implications for Practice: The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration‐approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low‐dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies.

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Long‐term therapeutic efficacy and toxicity of recombinant interferon‐alpha 2a in polycythaemia vera

Cited by 21 publications

References 12 publications

RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition

RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition

New Perspectives on Polycythemia Vera: From Diagnosis to Therapy

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

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