A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma
| العنوان: | A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma |
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| المؤلفون: | Marc André, Peter Vandenberghe, Laurent Knoops, Aspasia Stamatoullas, Ioanna-Andrea Stoian, Oumedaly Reman, Eric Van Den Neste, Sarah Bailly, Olivier Casasnovas, Herve Ghesquieres, Romain Dubois, Corinne Haioun, Marie-José Claessen, Franck Morschhauser, Thomas Gastinne, Gregor Verhoef, Marie-Christine Copin, Hélène Poirel, Amine Belhabri, A. Cottereau |
| المساهمون: | Cliniques Universitaires Saint-Luc [Bruxelles], CHU UCL Namur, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Henri Mondor, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Hospitals Leuven [Leuven], Erasmus University Rotterdam, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, CHU Henri Mondor [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinical Haematology, Hematology, Université de Lille, CHU Lille, CNRS, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Centre hospitalier universitaire de Nantes [CHU Nantes], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel], Université Claude Bernard Lyon 1 [UCBL], Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T], Mouvement, Équilibre, Performance, Santé [MEPS], Université Catholique de Louvain = Catholic University of Louvain [UCL], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA] |
| المصدر: | Haematologica Haematologica, Ferrata Storti Foundation, 2018, 108 (5), pp.840-847. ⟨10.3324/haematol.2017.180554⟩ Haematologica, 2018, 108 (5), pp.840-847. ⟨10.3324/haematol.2017.180554⟩ Haematologica, 103(5), 840-848. Ferrata Storti Foundation |
| بيانات النشر: | Ferrata Storti Foundation (Haematologica), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Ruxolitinib, Administration, Oral, Salvage therapy, Phases of clinical research, Gastroenterology, 0302 clinical medicine, hemic and lymphatic diseases, Aged, 80 and over, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Prognosis, Hodgkin Disease, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Article, Young Adult, 03 medical and health sciences, Internal medicine, Nitriles, medicine, Refractory Hodgkin Lymphoma, Humans, Adverse effect, Protein Kinase Inhibitors, Survival rate, Aged, Salvage Therapy, Hodgkin Lymphoma, business.industry, Janus Kinase 1, Janus Kinase 2, medicine.disease, Discontinuation, Pyrimidines, 030104 developmental biology, Drug Resistance, Neoplasm, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pyrazoles, Neoplasm Recurrence, Local, business, Follow-Up Studies |
| الوصف: | International audience; JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in patients with relapsed/refractory Hodgkin lymphoma. The primary objective was overall response rate according to the International Harmonization Project 2007 criteria. Thirty-three patients with advanced disease (median number of prior lines of treatment: 5; refractory: 82%) were included; nine (27.3%) received at least six cycles of ruxolitinib and six (18.2%) received more than six cycles. The overall response rate after six cycles was 9.4% (3/32 patients). All three responders had partial responses; another 11 patients had transient stable disease. Best overall response rate was 18.8% (6/32 patients). Rapid alleviation of B-symptoms was common. The median duration of response was 7.7 months, median progression-free survival 3.5 months (95% CI: 1.9-4.6), and the median overall survival 27.1 months (95% CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%). One event led to treatment discontinuation, while 87.5% of patients recovered without sequelae. Twenty-five adverse events were grade 3 or higher. These events were mostly anemia (n=11), all considered related to ruxolitinib. Other main causes of grade 3 or higher adverse events included lymphopenia and infections. Of note, no cases of grade 4 neutropenia or thrombocytopenia were observed. Ruxolitinib shows signs of activity, albeit short-lived, beyond a simple anti-inflammatory effect. Its limited toxicity suggests that it has the potential to be combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005. |
| وصف الملف: | Print-Electronic; application/pdf; application/octet-stream; application/rdf+xml; charset=utf-8 |
| تدمد: | 1592-8721 0390-6078 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f54b4b9202cf10319a1fd76b320dfcc3Test https://doi.org/10.3324/haematol.2017.180554Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f54b4b9202cf10319a1fd76b320dfcc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15928721 03906078 |
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