Ruxolitinib salvage therapy is effective for steroid‐refractory graft‐versus‐host disease in children: A single‐center experience

Abstract

Background Despite the increasing performance of allogeneic hematopoietic cell transplantation over the last decades, graft‐versus‐host disease (GVHD) remains the main cause of morbidity and mortality. The efficacy of ruxolitinib against GVHD has been demonstrated in adult studies; however, very few studies have been conducted in children. Procedure This study aimed to evaluate the efficacy of ruxolitinib in 29 children with steroid‐refractory acute or chronic GVHD. Twenty‐five (87%) patients received at least three different immune modulator agents, including methylprednisolone, before initiating ruxolitinib. Results All grade 2 acute GVHD patients completely responded to ruxolitinib treatment; 82% of high‐grade (3‐4) acute GVHD patients and 80% of chronic GVHD (moderate‐severe) patients had at least a partial response. Of seven patients with bronchiolitis obliterans, five had a partial response after ruxolitinib. Of 29 patients, 22 were administered steroids at any time in the first month of acute GVHD or the first three months of chronic GVHD during ruxolitinib usage, which was significantly tapered by the end of the observation period. Conclusion Steroid‐refractory acute and chronic pediatric GVHD patients treated with ruxolitinib had a high overall response rate, with the additional benefit of steroid sparing.

Ruxolitinib As a Salvage Therapy for Acute and Chronic Graft-versus-Host Disease in Children and Young Adults: a single institution experience

“…In our cGvHD group, our CR (22%) was similar to that reported in other pediatric studies, while our ORR (67%) was lower 17,18,20 . The reduction in ORR was not due to increased disease severity, as this was similar to other studies, but may reflect the small number of heterogenous patients in these reports, differences in co-administration of other immunosuppressive drugs, and/or variations in response criteria.…”

“…However, our results were similar to the week 4 outcomes published by Khandelwal et al on 13 pediatric patients with SR-aGvHD (45% ORR, 9% CR) 16 . The best response achieved in our cohort of patients with SR/SD-aGvHD (80% ORR) was similar to that reported in other pediatric and adult studies 3,4,[16][17][18][19][20] . Though comparisons are difficult given the small number of patients with aGvHD in our study, the lower response rate at day 28 in pediatric patients as compared to adults may be due to the uncertainty of dosing in pediatric patients who may have increased clearance of the drug, and as we gradually increased the dose of ruxolitinib over time, this practice may take longer to achieve therapeutic levels compared to adult patients.…”

“…This study included only 12 pediatric patients, and it is not clear how many were on the ruxolitinib arm, as the full results have not been published to date. This, combined with the limited data currently available regarding the use of ruxolitinib in the pediatric and YA population [16][17][18][19][20] , highlights the need for ongoing reporting of results with ruxolitinib use in this age group.…”

Ruxolitinib for Treating Steroid-Refractory Acute Graft-Versus-Host Disease in an Infant with Malignant Osteopetrosis Who Received Double-Unit Umbilical Cord Blood Transplantation

“…Ruxolitinib (10 mg twice daily) showed significant improvements in efficacy in a multicenter, randomized, open-label, phase 3 trial in patients ≥ 12 years with steroid refractory acute GVHD after allogenic stem cell transplantation [15]. Salvage treatment with ruxolitinib for steroid refractory GVHD in children has been reported as a retrospective study abroad [16][17][18]. The pediatric dosing of ruxolitinib for GVHD is not established yet.…”

Janus Kinase Inhibitors and Cell Therapy

“…Several published studies also support these findings, where ruxolitinib was given to refractory GVHD patients and are summarized in Table 1. These includes reports in adults (71-74, 76, 77, 79, 82) and pediatric patients (70,75,(77)(78)(79)(80)(81)(82), SR-aGVHD (70,71,73,75,(77)(78)(79)(80)(81) as well as SR-cGVHD (71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82).…”