Soluble interleukin-2 receptor α activation in a Children's Oncology Group randomized trial of interleukin-2 therapy for pediatric acute myeloid leukemia

Abstract

Purpose: To assess associations of soluble IL-2 receptor alpha (sIL-2rα) concentration with outcomes in pediatric acute myeloid leukemia (AML) in a phase 3 trial of IL-2 therapy.

Procedures: We randomized 289 children with AML in first remission after intensive chemotherapy to receive IL-2 infused on days 0-3 and 8-17 (IL-2 group) or no further therapy (AML control group). We measured sequential serum sIL-2rα concentrations in both groups before, during and after therapy in both groups and in reference controls without AML.

Results: Before treatment, mean sIL-2rα concentrations were similar in the IL-2 group and AML controls, but significantly higher than in reference controls. Both AML groups experienced reduction in sIL-2rα concentration after chemotherapy. Thereafter in the IL-2 group, mean sIL-2rα concentration increased from 2,669 pg/ml before IL-2 to 15,534 pg/ml on day 4 (P < 0.001) and 10,585 pg/ml on day 18 (P < 0.001). In the control group sIL-2rα concentration did not change after 28 days of follow-up. Five-year disease-free survival (DFS) was 51% in the IL-2 group and 58% in the controls (P = 0.489) and overall survival was 70% and 73%, respectively (P = 0.727).

Conclusion: SIL-2rα concentration was elevated in AML at diagnosis and tended to normalize after chemotherapy. IL-2 infusion significantly increased sIL-2rα concentration, but did not improve DFS or survival in pediatric AML. Furthermore, sIL-2rα concentration was not predictive of outcome before, during or after treatment for AML.

Figure 1

Treatment schema for CCG-2961 and schedule of interleukin-2 (IL-2) infusions (inset) and sampling for serum IL-2 receptor (block arrows). IdaCTER is idarubicin, cytarabine, thioguanaine, etoposide, and rubidomycin (daunorubicin), HidAC is High dose Ara-C, L-asp is L-asparaginase and R is randomization.

Figure 2

Actuarial five-year disease-free survival and overall survival of randomized patients.

Figure 3

Actuarial disease-free survival of Interleukin-2 group and control group according to Phase 2 randomization to IDADCTER (idarubicin, cytarabine, thioguanine, etoposide, and daunorubicin) and FLU IDA (fludarabine monophosphate, cytarabine and idarubicin)

Figure 4

Comparison of sequential changes in median concentration of serum soluble IL-2 receptor alpha over time in the IL-2 group and control group. Time 1 is on study); time 2 is post chemotherapy (pre-IL-2 for IL-2 group and day 0 for control); time 3 = day 4 of IL-2 for IL-2 group; Time 4 is day 18 of IL-2 for IL-2 group and d 28 follow-up for controls.