Phase 1-2 trial of IL15-activated cytokine-induced killer cells after allogeneic hematopoietic stem-cell transplantation in high-risk leukemia

Patients with high-risk (HR) leukemia remain at substantial risk of early relapse, treatment-related toxicity, and poor survival, underscoring the need for effective relapse prevention therapies. The first-in-human, disease burden-guided EudraCT 2013-005446-11 study at the Goethe University Frankfurt (Germany) evaluated the feasibility, safety, and efficacy of donor-derived allogeneic interleukin-15-activated cytokine-induced killer cells (IL15-CIK) combining T-cell and natural killer cell properties for post-transplant disease control. The study included 53 adult and pediatric patients with HR leukemia, who received 56 courses of IL15-CIK monotherapy after HLA-matched or HLA-mismatched transplantation. Treatment intent was categorized as consolidation (13%), preemptive (61%), or salvage (27%), with 169 infusions administered as a single dose (29%) or according to adaptable dose-escalation regimens (71%). Acute graft-versus-host disease (GVHD) grades 1-2 and grade 3 occurred in 27% and 4% of cases, respectively; no extensive chronic GVHD or treatment-related mortality was observed. IL15-CIK-associated adverse events were predominantly mild. Disease clearance (cumulative incidence of complete molecular remission) peaked at day 700, reaching 74% in the preemptive and 13% in the salvage setting. The five-year progression-free survival rate was 50% overall and highest (69%) in pediatric AML. The five-year overall survival rate was 71% in the consolidation, 61% in the preemptive, and 20% in the salvage setting. The authors conclude that IL15-CIK monotherapy is feasible and safe and demonstrates promising relapse-preventive activity after hematopoietic stem-cell transplantation in HR leukemia.