1. Phase II study of oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.
- Author
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UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service de médecine nucléaire, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/DDUV/GECE - Génétique cellulaire, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Van Den Neste, Eric, André, Marc, Gastinne, Thomas, Stamatoullas, Aspasia, Haioun, Corinne, Belhabri, Amine, Reman, Oumedaly, Casasnovas, Olivier, Guesquieres, Hervé, Verhoef, Gregor, Claessen, Marie-José, Poirel, Hélène, Copin, Marie-Christine, Dubois, Romain, Vandenberghe, Peter, Stoian, Ioanna-Andrea, Cottereau, Anne S, Bailly, Sarah, Knoops, Laurent, Morschhauser, Franck, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service de médecine nucléaire, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/DDUV/GECE - Génétique cellulaire, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Van Den Neste, Eric, André, Marc, Gastinne, Thomas, Stamatoullas, Aspasia, Haioun, Corinne, Belhabri, Amine, Reman, Oumedaly, Casasnovas, Olivier, Guesquieres, Hervé, Verhoef, Gregor, Claessen, Marie-José, Poirel, Hélène, Copin, Marie-Christine, Dubois, Romain, Vandenberghe, Peter, Stoian, Ioanna-Andrea, Cottereau, Anne S, Bailly, Sarah, Knoops, Laurent, and Morschhauser, Franck
- Abstract
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 HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27.3%) received at least 6 cycles of ruxolitinib and six (18.2%) > 6 cycles therapy. The overall response rate after 6 cycles was 3/32 (9.4%) patients, all partial responders, with transient stable disease in 11/32. Best overall response rate was 6/32 (18.8%). Rapid alleviation of B-symptoms was commonly noted. Median response duration was 7.7 months, median progression-free survival 3.5 months (95%CI: 1.9-4.6), and median overall survival 27.1 months (95%CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%); one led to treatment discontinuation; 87.5% recovered without sequelae. Twenty-five were of > Grade3. The latter consisted mostly of anemia (n=11) all considered related to ruxolitinib. Other main causes of > Grade3 adverse events included lymphopenia and infections. Of note, there was no Grade4 neutropenia or thrombocytopenia observed. Ruxolitinib shows signs of activity, though short-lived, beyond simple anti-inflammation. Its limited toxicity suggests the potential of being combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005.
- Published
- 2018