Ruxolitinib Is Promising in Pediatric Chronic GVHD


Ruxolitinib, when administered using a pediatric dosing algorithm, was found to elicit responses in patients with chronic graft-versus-host disease with acceptable safety.

Ruxolitinib (Jakafi), when administered using a pediatric dosing algorithm, was found to elicit responses in patients with chronic graft-versus-host disease (GVHD) with acceptable safety, according to preliminary findings from a retro review presented during the 2021 Transplantation & Cellular Therapy Meeting.1

The FDA approved ruxolitinib for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older in 2019 based on its ability to achieve a high rate of objective responses, as seen in Study INCB 18424-271 (NCT02953678). Despite this progress, there are limited data and understanding on how to administer ruxolitinib in patients with chronic disease and specifically how to dose the drug.2

A retrospective review of 20 patients with chronic GVHD, 4 of whom presented with overlap syndrome was conducted with the goal of providing more understanding on dosing ruxolitinib in pediatric patients with chronic GVHD. Investigators led by YunZu Michele Wang, MD, member, Division of Bone Marrow Transplantation and Immune Deficiency and instructor, Department of Pediatrics at the University of Cincinnati in Ohio, followed a weight-based dosing algorithm by which patients < 25 kg received 2.5 mg of ruxolitinib twice daily and those whose weight was ≥ 25 kg received at 5 mg dose of ruxolitinib twice daily. Patients in the study who were also being treated with tri-azole antifungal therapy had a 50% dose reduction of ruxolitinib upfront. The study protocol allowed for progressive dose increases of up to 10 mg twice daily. Response to ruxolitinib was assessed at the time of therapy initiation as well as a minimum of 30 days after treatment was initiated. Responses were evaluated per the National Institutes of Health 2014 Criteria.

The study population was compiled of patients aged 5 to 26 years. At baseline, information obtained for each patient showed that the underlying disease in the population was beta-thalassemia, DNA ligase intravenous deficiency, chronic neutrophilic leukemia, myelodysplastic syndrome, B-cell acute lymphoblastic leukemia (ALL), Epstein-Barr Virus, and hemophagocytic lymphohistiocytosis, acute myeloid leukemia, chronic disease, hemoglobin sickle cell disease, T-cell ALL, hyper-IgM syndrome, Fanconi anemia, and chronic myeloid leukemia.

Sixteen of the patients were steroid-refractory, but there were also 4 steroid-dependent patients included in the study. As prior systemic therapy, patients received a wide range of agents, some of which were rituximab (Rituxan), imatinib (Gleevec), infliximab (Remicade), and ibrutinib (Imbruvica). Most patients had also received a steroid.

Further assessment of disease characteristics in these patients showed that for the majority, chronic GVHD had affected major organs. The skin was the site of the most impact, which was observed in 11 patients. In addition, the eyes or sclerotic skin were impacted in 7 patients each, the gastrointestinal tract was affected in 6 patients, and the lungs, liver, and genitourinary system were impacted in 3 patients each. There were 2 patients whose joints were affected by their chronic GVHD and 1 whose muscles were compromised.

At the time of ruxolitinib initiation, 16 patients were also on treatment with prednisone at a median dose of 0.5 mg/kg daily (range, 0.08 mg-1.5 mg). The median time from diagnosis to ruxolitinib dosing was 181 days (range, 17-1792 days). Ruxolitinib was administered at a median dose level of 5 mg daily (range, 2.5 mg-10 mg). Notably, 6 patients in the study received the maximum daily ruxolitinib allotment of 20 mg.

Wang et al observed a response to ruxolitinib in the skin, joints, gastrointestinal tract, liver, and muscles. A 100% response rate was observed in the group of patients with sclerotic skin chronic GVHD. In addition, 2 out of 3 patients who had lung involvement experienced pulmonary function test stabilization following treatment with ruxolitinib.

Of the responses elicited by ruxolitinib therapy, 2 were complete responses in the skin, and 12 were partial responses that occurred a median of 48 days from the time ruxolitinib was first dosed. The overall response rate observed with ruxolitinib in this study was 70%. Durable responses were achieved by 13 of the 14 responders at a median of 411 days. There was also 1 patient who achieved stable disease. In the group of 16 patients who were on steroids at the time of ruxolitinib initiation, 13 patients were in the process of being weaned or were off steroids at data cutoff. Overall, 18 patients from the 20-patient cohort were still alive at data cutoff. Wang et al observed progressive disease in 4 of the study subjects, and 2 patients died from chronic GVHD that had severely progressed.

Ruxolitinib demonstrated some ability to activate the JAK/STAT pathway in this study, according to flow cytometry histograms taken before treatment and after initiation of treatment. The in vitro data showed fewer cases of progressive disease after ruxolitinib.

Ten patients in the study experienced adverse events (AEs) of any grade. In some cases of grade 3 or higher AEs, Wang et al intervened by holding off on treatment. In the case of grade 3 neutropenia, however, the dose of ruxolitinib was reduced. Another intervention involved holding the concurrent myelosuppressive agent in a patient who had Enterobacter bacteremia, methicillin-sensitive Staphylococcus aureus, grade 3 thrombocytopenia, and grade 4 neutropenia. The final intervention of note involved starting a patient with an E coli urinary tract infection, C difficile colitis, grade 4 thrombocytopenia, and grade 2 neutropenia on a thrombopoietin receptor agonist.

Notably, none of the study subjects developed a fungal infection or pneumocystis pneumonia while receiving ruxolitinib. There was also no infection caused by neutropenia or bleeding caused by thrombocytopenia.

Findings from this retrospective analysis imply that ruxolitinib is safe and tolerable in children with chronic GVHD. Wang et al note that high infection rates are an ongoing problem for the chronic GVHD population and based on this analysis, it is still unclear whether or not ruxolitinib increases the rate of infection for patients with chronic GVHD.


  1. Wang YM, Teusink-Cross A, Elborai Y, et al. Ruxolitinib for the treatment of chronic gvhd in children and young adults. Presented at: Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; virtual. Abstract 298.
  2. FDA approves ruxolitinib for acute graft-versus-host disease. New release. FDA. May 24, 2019. Accessed February 9, 2021.

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