Safety Analysis of Patients Who Received Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft-Vs-Host Disease in Expanded Access Programs

Abstract

Introduction Graft-vs-host disease (GVHD) is a serious, potentially fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ruxolitinib (RUX), a Janus kinase (JAK)1/JAK2 inhibitor, is in phase 3 development for patients with steroid-refractory (SR) acute and chronic GVHD. Outside of clinical trials, access to RUX is provided to patients with GVHD through Incyte- and Washington University (WU)–sponsored expanded access programs (EAPs) and single-patient investigational new drug (IND) applications. Objective To report pooled safety data from a subset of patients with SR acute GVHD (aGVHD) enrolled in these programs. Methods Eligible patients were ≥12 years of age, developed SR acute or chronic GVHD after allo-HSCT, and were not eligible for Incyte-sponsored GVHD clinical trials. Patients enrolled in the 2 EAPs received oral RUX at a starting dose of 5 mg twice daily (BID; maximum dose 10 mg BID); those on single-patient INDs received RUX as agreed to by Incyte and the treating physician. Concurrent therapy with other treatments for GVHD was permitted. Serious adverse events (SAEs) were assessed. Data from patients with aGVHD were pooled across the 3 programs; summary statistics are reported. Results At data cutoff (02 Apr 2018), 28 patients with SR aGVHD (Incyte EAP, n=13; WU EAP, n=9; single-patient IND, n=6) and 104 patients with SR chronic GVHD (Incyte EAP, n=33; WU EAP, n=31; single-patient IND, n=40) had enrolled in the programs. Mean (range) age of patients with SR aGVHD was 48 (13–73) years; 71.4% of patients were male. aGVHD was reported in the gastrointestinal (GI) tract (57.1%), skin (53.6%), liver (17.9%), lungs (7.1%), and eyes (3.6%). Most patients (75.0%) received ≥3 prior treatments for GVHD, including corticosteroids; 71.4% of patients received calcineurin inhibitors, and 28.6% of patients received prior RUX. Most patients (n=25) initially received 5 mg RUX BID; 1 patient received 10 mg RUX BID, and 2 patients received RUX 5 mg once daily. Five patients (17.9%) received 10 mg RUX BID as their last dose. Treatment was ongoing in 13 patients (46.4%) at data cutoff; discontinuations were due to death (n=7), withdrawn consent (n=3), disease progression (n=2), primary disease relapse (n=2), or drug refusal (n=1). The mean (range) duration of treatment was 79.6 (1–326) days. SAEs were reported in 13 patients (46.4%). There were no cytopenia, fungal infection, or cytomegalovirus SAEs. Respiratory failure (n=3) and GVHD (n=2) were the only SAEs reported in >1 patient. Ten patients had fatal outcomes following an SAE. Sepsis (n=1) was the only fatal SAE suspected to be related to RUX; no others SAEs were considered related to RUX. Conclusion Patients in the RUX EAPs were heavily pretreated, and more than half of the patients reported GI GVHD. SAEs were reported in almost half of the patients (46.4%), but no new or unexpected SAEs have been reported.