Real-world experience with low-dose IL-2 for children and young adults with refractory chronic graft-versus-host disease

The majority of patients with chronic graft-vs-host disease are steroid refractory (SR-cGVHD), creating a need for safe and effective therapies. Subcutaneous low-dose interleukin-2 (LD IL-2), which preferentially expands CD4+ regulatory T cells (Treg), has been evaluated in 5 clinical trials at our center with partial responses (PR) in ~50% of adults and 82% of children by week 8. We now report additional real-world experience with LD IL-2 in 15 children and young adults. We conducted a retrospective chart review of patients with SR-cGVHD at our center who received LD IL-2 from August, 2016 to July, 2022 not on a research trial. The median age at start of LD IL-2 was 10.4 years (range 1.2, 23.2) at a median of 234 days from cGVHD diagnosis (range 11, 542). Patients had median 2.5 (range 1, 3) active organs at LD IL-2 start and received median 3 (range 1, 5) prior therapies. The median duration of LD IL-2 therapy was 462 days (range 8, 1489). Most patients received 1 × 106 IU/m2/day. There were no serious adverse effects. The overall response rate in 13 patients who received >4 weeks of therapy was 85% (5 complete response, 6 PR) with responses in diverse organs. Most patients significantly weaned corticosteroids. Treg preferentially expanded with a median peak fold increase in Treg:CD4+ conventional T cell ratio of 2.8 (range 2.0, 19.8) by 8 weeks on therapy. LD IL-2 is a well-tolerated, steroid-sparing agent with a high response rate in children and young adults with SR-cGVHD.