Abstract
Summary
Ruxolitinib (JAKAFI®) is a Janus kinase (JAK) 1 and JAK2 inhibitor that is approved for acute and chronic graft-versus-host disease (GVHD). The phase III REACH2 and REACH3 trials tested efficacy and safety of ruxolitinib for patients with acute and chronic GVHD, respectively, who were no longer responding to steroids. This summary describes additional analyses from REACH2 and REACH3 that evaluated the effect of treatment initiation time, use of antifungal azole treatments, and development of cytopenias (low number of blood cells) on ruxolitinib effectiveness.
Results from REACH2 and REACH3 were analyzed to inform whether time to start treatment, use of azoles, and developing cytopenias affected how well ruxolitinib worked. Treatment effectiveness was measured as any response to treatment, including complete resolution of all GVHD symptoms.
When analyzing time to start treatment, more patients taking ruxolitinib had a better response than those taking control treatments, regardless of when treatment started. In acute GVHD, treatment responses generally appeared higher when ruxolitinib was started early (within 3 days of steroids not working). The effectiveness of ruxolitinib persisted even among patients taking azoles or for patients who developed cytopenias, with some patients having their dosage adjusted.
The treatment benefit of ruxolitinib compared with control treatments is consistently observed across patients with acute and chronic GVHD who no longer respond to steroids, regardless of time to start of treatment, use of azoles, or developing cytopenias. Dose modifications of ruxolitinib may need to occur to ensure treatment is well tolerated.
Footnotes
Acknowledgements
The authors of this article thank the patients who participated in these trials and their families, as well as the investigators, co-investigators, and clinical site staff. Plain language writing and editorial assistance were provided by Aarthi Gobinath, PhD, CMPP, from Round Hill, part of The Lockwood Group (Stamford, CT, USA), and funded by Incyte Corporation (Wilmington, DE, USA).
Ethics approval and consent to participate
Based on the retrospective post hoc analyses presented in this summary, no additional ethical approval or consent to participate was required. However, the REACH trials that provided the data for these analyses were designed and conducted in accordance with the International Council for Harmonisation Guideline for Good Clinical Practice, Declaration of Helsinki, and local regulatory requirements. Study protocols were approved by institutional review boards at each site. Patients or their guardians provided written informed consent for participation in the original REACH trials.
Author contributions
Zahra Mahmoudjafari and Robert Zeiser: conceptualization; writing – review and editing. Valkal Bhatt, Zhenyi Xue and Gérard Socié: conceptualization; formal analysis; writing – review and editing. Franco Locatelli: formal analysis; writing – review and editing.
Funding
The analyses were funded by Incyte Corporation (Wilmington, DE, USA).
Competing interests
Zahra Mahmoudjafari: Advisory board participation: Bristol Myers Squibb, Genentech, Janssen, Kite, Pfizer. Valkal Bhatt: employee and shareholder of Incyte Corporation. Zhenyi Xue: employee and shareholder of Incyte Corporation. Franco Locatelli: consulting fees and speaker bureau: Amgen, Gilead, Miltenyi Biotec, Novartis, Sanofi, Sobi. Gérard Socié: consulting fees and speaker bureau: AlloVir, Incyte Corporation, Novartis, Sanofi. Robert Zeiser: consulting fees and speaker bureau: Incyte Corporation, medac, Mallinckrodt Pharmaceuticals/Therakos, Neovii, Novartis, Sanofi.
Availability of data and materials
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