Low-Dose Interleukin-2 for Pediatric Steroid-Refractory Chronic Graft-Versus-Host Disease

By Dustin Samples - February 21, 2023

Chronic graft-versus-host disease (cGVHD) can become steroid refractory, so there is a need for second-line therapies to reduce steroid reliance. One previously studied treatment is subcutaneous low-dose (LD) interleukin-2 (IL-2). At the Dana-Farber Cancer Institute, children and adults have previously demonstrated partial responses (PR) to LD IL-2 at approximately 8 weeks.

At the 2023 Tandem Meetings of the ASTCT and CIBMTR, researchers from the Dana-Farber Cancer Institute presented their real-world findings of subcutaneous LD IL-2 for children with steroid-refractory cGVHD.

From August 2016-July 2022, 15 children with steroid-refractory cGVHD underwent treatment with subcutaneous LD IL-2 (median age, 10.4 years old). All had moderate-severe cGVHD with an average of 2.3 organs involved. The median time from diagnosis to the start of IL-2 therapy was 234 days. Four patients received reduced doses (3 due to malaise and 1 due to thrombocytopenia), and the rest received the institution’s previously demonstrated maximum dose of 1x106IU/m2/day. The median time of LD IL-2 treatment was 462 days.

No serious adverse events occurred attributable to therapy with LD IL-2. During the study period, 2 patients died (1 due to advanced hepatic dysfunction and 1 due to poor graft function) and the remaining 13 children had an overall response rate of 85% after at least 8 weeks of therapy. There were only 3 children with a complete response, but 8 had a partial response, and 2 others demonstrated stable disease. Of the patients with a partial response, 4 had complete responses specific to 1 or more tissue systems.

“As expected, Treg expanded preferentially with a peak fold increase in Treg:CD4+ conventional T cell (Tcon) ratio of 2.83 (IQR: 2.55, 5.11) by 2 months on therapy,” the authors said. “Treg expansion did not appear to be impacted by steroids (median dose at start 0.79mg/kg/d), ruxolitinib (n=2; 10-20mg daily), or calcineurin inhibitors (n=3; standard dosing).”

Of the 13 evaluable patients, 12 were able to significantly reduce their steroid dose.

“Our data support a growing body of evidence that LD IL-2 is a safe, well-tolerated, steroid-sparing agent with a high response rate in children, including CRs for cutaneous cGVHD,” the researchers concluded.

Wobma H, Kapadia M, Calderon FA, et al. Real-World Experience with Low Dose Interleukin-2 for Children with Steroid Refractory Chronic Graft Vs Host Disease. Abstract #347. Presented at the 2023 Tandem Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL.

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