Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease

dc.contributor.authorZeiser, Robert
dc.contributor.authorPolverelli, Nicola
dc.contributor.authorRam, Ron
dc.contributor.authorHashmi, Shahrukh K.
dc.contributor.authorChakraverty, Ronjon
dc.contributor.authorMiddeke, Jan Moritz
dc.contributor.authorMusso, Maurizio
dc.contributor.authorGiebel, Sebastian
dc.contributor.authorUzay, Ant
dc.contributor.authorLangmuir, Peter
dc.contributor.authorHollaender, Norbert
dc.contributor.authorGowda, Maanasa
dc.contributor.authorStefanelli, Tommaso
dc.contributor.authorLee, Stephanie J.
dc.contributor.authorTeshima, Takanori
dc.contributor.authorLocatelli, Franco
dc.contributor.authorInvestigators, REACH3
dc.date.accessioned2023-02-21T12:41:59Z
dc.date.available2023-02-21T12:41:59Z
dc.date.issued2021-01-01
dc.description.abstractBackground Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50\% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD. Methods This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24
dc.description.abstractkey secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24. Results A total of 329 patients underwent randomization
dc.description.abstract165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7\% vs. 25.6\%
dc.description.abstractodds ratio, 2.99
dc.description.abstractP<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months
dc.description.abstracthazard ratio, 0.37
dc.description.abstractP<0.001) and higher symptom response (24.2\% vs. 11.0\%
dc.description.abstractodds ratio, 2.62
dc.description.abstractP=0.001). The most common (occurring in <greater than or equal to>10\% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2\% in the ruxolitinib group and 10.1\% in the control group) and anemia (12.7\% and 7.6\%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups. Conclusions Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte
dc.description.abstractREACH3 ClinicalTrials.gov number, NCT03112603.) Ruxolitinib for Chronic Graft-versus-Host Disease Standard treatment for GVHD is glucocorticoids, but for glucocorticoid-refractory GVHD, no intervention has emerged as standard second-line treatment. This trial with 329 patients compared ruxolitinib with control (chosen from among 10 possible therapies) in patients with glucocorticoid-refractory chronic GVHD. Response at week 24 was 50\% with ruxolitinib as compared with 26\% with control therapy.
dc.description.issue3
dc.description.issueJUL 15
dc.description.pages228-238
dc.description.volume385
dc.identifier.doi10.1056/NEJMoa2033122
dc.identifier.urihttps://hdl.handle.net/11443/2772
dc.identifier.urihttp://dx.doi.org/10.1056/NEJMoa2033122
dc.identifier.wosWOS:000675631800011
dc.publisherMASSACHUSETTS MEDICAL SOC
dc.relation.ispartofNEW ENGLAND JOURNAL OF MEDICINE
dc.titleRuxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease
dc.typeArticle

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