Phase II study of oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.
(2018) Haematologica : the hematology journal — Vol. 103, n° 5, p. 840-848 (2018)
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- 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.
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Van Den Neste, E., André, M., Gastinne, T., Stamatoullas, A., Haioun, C., Belhabri, A., Reman, O., Casasnovas, O., Guesquieres, H., Verhoef, G., Claessen, M.-J., Poirel, H., Copin, M.-C., Dubois, R., Vandenberghe, P., Stoian, I.-A., Cottereau, A. S., Bailly, S., Knoops, L., & Morschhauser, F. (2018). Phase II study of oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma. Haematologica : the hematology journal, 103(5), 840-848. https://doi.org/10.3324/haematol.2017.180554 (Original work published 2018)