• Robert Zeiser, Nikolas von Bubnoff, Jason Butler, Mohamad Mohty, Dietger Niederwieser, Reuven Or, Jeff Szer, Eva M Wagner, Tsila Zuckerman, Bruyère Mahuzier, Judith Xu, Celine Wilke, Kunal K Gandhi, Gérard Socié, and REACH2 Trial Group.
• From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).
• N. Engl. J. Med. 2020 May 7; 382 (19): 1800-1810.

BackgroundAcute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD.MethodsWe conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56.ResultsA total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]).ConclusionsRuxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy. (Funded by Novartis; REACH2 ClinicalTrials.gov number, NCT02913261.).Copyright © 2020 Massachusetts Medical Society.

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