Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study

Kiladjian, Jean Jacques; Zachée, Pierre; Hino, Masayuki; Pane, Fabrizio; Masszi, Tamás; Harrison, Claire; Mesa, Ruben A.; Miller, Carole B.; Passamonti, Francesco; Durrant, Simon; Grießhammer, Martin; Kirito, Keita; Besses, Carlos; Moiraghi, Beatriz; Rumi, Elisa; Rosti, Vittorio; Blau, Igor Wolfgang; Francillard, Nathalie; Dong, Tuochuan; Wroclawska, Monika; Vannucchi, Alessandro M.; Verstovšek, Srđan

doi:10.1016/s2352-3026(19)30207-8

Cited by 104 publications

(90 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ruxolitinib is a JAK1 and JAK2 inhibitor with potent anti-inflammatory properties and excellent safety profile, that is approved for the treatment of myelofibrosis [12,13] and polycythemia vera [14,50,51]; remarkably, ruxolitinib proved to be efficacious in conditions characterized by exaggerated release of inflammatory cytokines and activation of immunocompetent cells, such as the hemophagocytic lymphohistiocytosis [15] and the graft-versus-host disease in recipients of allogeneic hematopoietic stem cell transplantation [16]. We describe here results of a prospective, observational study in 34 patients with severe pulmonary manifestations of COVID-19, not requiring mechanical ventilation, who received compassionate-use ruxolitinib within a treatment protocol approved by Italian Agency for Drugs.…”

Section: Discussionmentioning

confidence: 99%

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

et al. 2020

View full text Add to dashboard Cite

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/ JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus highflow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

show abstract

Section: Discussionmentioning

confidence: 99%

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In the ruxolitinib arm, a higher risk for non-melanoma skin cancer was observed [79]. At 5 years of follow-up, 98% of patients initially assigned to BAT crossed over to ruxolitinib, with a probability of survival at 5 years of 91.9% with ruxolitinib and 91.0% with BAT [80]. In the RESPONSE-2 open-label phase IIIb study, efficacy and safety of ruxolitinib versus BAT were assessed in 149 PV patients without palpable splenomegaly resistant or intolerant to HU; BAT included HU (49% of subjects) and IFN or PEG-IFN (13% of subjects).…”

Section: Ruxolitinibmentioning

confidence: 99%

New Perspectives on Polycythemia Vera: From Diagnosis to Therapy

Iurlo

Cattaneo

Bucelli

et al. 2020

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…Thromboembolic complications are highly relevant in critically ill CoVID-19 patients, where coagulation abnormalities are frequently reported and correlate with dismal prognosis. In contrast, the use of ruxolitinib has shown protective effects regarding thromboembolic events in preclinical studies [20] and advanced clinical trials [21]. Inhibitors of specific cytokine signaling pathways such as the IL6 receptor antibody tocolizumab have also been studied in CoVID-19 with variable success.…”

mentioning

confidence: 99%

Holding CoVID in check through JAK? The MPN-approved compound ruxolitinib as a potential strategy to treat SARS-CoV-2 induced systemic hyperinflammation

Heidel

Hochhaus

2020

Leukemia

View full text Add to dashboard Cite

Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study

Cited by 104 publications

References 19 publications

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

New Perspectives on Polycythemia Vera: From Diagnosis to Therapy

Holding CoVID in check through JAK? The MPN-approved compound ruxolitinib as a potential strategy to treat SARS-CoV-2 induced systemic hyperinflammation

Contact Info

Product

Resources

About