First-in-Human Study of IL15-Activated Cytokine-Induced Killer Cells After Allogeneic HCT Shows Durable Remission and Serotherapy-Associated Immune Reconstitution in Leukemia

Clinical Snapshot

Key Findings

• P Value: Not specified in abstract

• Effect Size: 5-year overall survival: 71% (consolidation), 61% (preemptive), 20% (salvage)

• Primary Outcome: Complete molecular remission rates: 74% (preemptive), 13% (salvage) at day 700

• Nnt Or Sensitivity: 5-year progression-free survival: 50% overall, 69% in pediatric AML

• Confidence Interval: Not reported in abstract

Clinical Application

Requires specialized cell processing facilities and expertise in adoptive immunotherapy Relevant to major Australian transplant centers; would require TGA approval for clinical use and consideration for PBS funding given specialized nature Adult and pediatric patients with high-risk leukemia post-allogeneic HSCT, particularly those suitable for preemptive therapy

Abstract

PURPOSE: 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. To our knowledge, this first-in-human, disease burden-guided study 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. METHODS: In a prospective, multicenter phase I/II trial (EudraCT 2013-005446-11) and an identically designed pilot study, 53 adult and pediatric patients with HR leukemia received 56 courses of IL15-CIK monotherapy after human leukocyte antigen (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%). RESULTS: 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, assessed by the 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 was 50% overall and highest (69%) in pediatric acute myeloid leukemia. The five-year overall survival (OS) was 71% in the consolidation, 61% in the preemptive, and 20% in the salvage setting. Multivariable analysis demonstrated significantly lower relapse rates with Campath compared with ATG, superior OS in myeloid malignancies, and reduced IL15-CIK efficacy in advanced disease. The median follow-up was 7.3 years. CONCLUSION: IL15-CIK monotherapy is feasible and safe and demonstrates promising relapse-preventive activity after hematopoietic stem-cell transplantation. Clinical outcomes are strongly influenced by disease burden at treatment initiation and previous serotherapy, supporting optimized patient selection and timing in future post-transplant immunotherapeutic strategies.

References

1. 1.Rettinger, E., Heckl, D., Hutter, M., Salzmann-Manrique, E., Luedtke, M., Huenecke, S., Bremm, M., Cappel, C., Bug, G., Greil, J., Meisel, R., Wagner-Drouet, E. M., Serve, H., Güngör, T., Klusmann, J. H., Klingebiel, T., Bader, P., & Bonig, H. (2026). First-in-Human Study of IL15-Activated Cytokine-Induced Killer Cells After Allogeneic HCT Shows Durable Remission and Serotherapy-Associated Immune Reconstitution in Leukemia. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01966