Phase II study of oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.

Van Den Neste, Eric [UCL] André, Marc [UCL] Gastinne, Thomas Stamatoullas, Aspasia Haioun, Corinne Belhabri, Amine Reman, Oumedaly Casasnovas, Olivier Guesquieres, Hervé Verhoef, Gregor Claessen, Marie-José Poirel, Hélène [UCL] Copin, Marie-Christine Dubois, Romain Vandenberghe, Peter Stoian, Ioanna-Andrea [UCL] Cottereau, Anne S Bailly, Sarah Knoops, Laurent [UCL] Morschhauser, Franck et al.[show all]

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.