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Ferrata Storti Foundation
Hodgkin Lymphoma
A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma
Haematologica 2018 Volume 103(5):840-848
Eric Van Den Neste,1 Marc André,2 Thomas Gastinne,3 Aspasia Stamatoullas,4 Corinne Haioun,5 Amine Belhabri,6 Oumedaly Reman, 7Olivier Casasnovas,8 Hervé Ghesquieres,9 Gregor Verhoef,10 Marie-José Claessen,11 Hélène A. Poirel,12 Marie-Christine Copin,13 Romain Dubois,13 Peter Vandenberghe,14 Ioanna-Andrea Stoian,15 Anne S. Cottereau,16 Sarah Bailly,1 Laurent Knoops17 and Franck Morschhauser18
Preliminary results were presented at the 58th Annual Meeting of the American Society of Hematology, held on December 3 – 6, 2016,
in San Diego, USA.
1Department of Hematology, Cliniques Universitaires Saint-Luc, UCL Brussels, Belgium; 2Hematology Department, CHU UCL Namur, Yvoir, Belgium; 3Hematology, CHU Nantes, France; 4Clinical Hematology, Centre Henri Becquerel, Rouen, France; 5Lymphoid Malignancies Unit, AP-HP, Groupe Hospitalier Mondor, Créteil, France; 6Onco-hematology, Centre Leon Berard, University Claude Bernard Lyon 1, France; 7Hematology, Centre Hospitalier Universitaire, Caen, France; 8Hematology Department, Hopital Le Bocage, CHU Dijon, France; 9Hospices Civils de Lyon, Université Claude Bernard, Centre Hospitalier Lyon- Sud, Pierre Bénite, France; 10Department of Hematology, University Hospitals Leuven, Belgium; 11Erasmus MC, Rotterdam, the Netherlands; 12Center for Human Genetics, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium; 13CHRU de Lille, France; 14Center for Human Genetics, Katholieke Universiteit - Leuven, Belgium; 15Nuclear Medicine, Cliniques Universitaires Saint-Luc, UCL Brussels, Belgium; 16Nuclear Medicine, Hôpital Tenon, Paris, France; 17Cliniques Universitaires Saint-Luc and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium and 18CHU Lille, Hematology Department, and Université de Lille, GRITA, France
ABSTRACT
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lym- phoma cells by recognizing JAK1-/JAK2-bound receptors. JAK block- ade 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 lym- phoma. 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 respon- ders had partial responses; another 11 patients had transient stable dis- ease. Best overall response rate was 18.8% (6/32 patients). Rapid allevia- tion 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 ruxoli- tinib. 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 ther- apeutic modalities. ClinicalTrials.gov: NCT01877005
Correspondence:
franck.morschhauser@chru-lille.fr
Received: September 12, 2017. Accepted: January 10, 2018. Pre-published: January 19, 2018.
doi:10.3324/haematol.2017.180554
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/5/840
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