A Phase 2 Trial of KIR-Mismatched Unrelated Donor Transplantation Using in Vivo T Cell Depletion with Antithymocyte Globulin in Acute Myelogenous Leukemia: Children’s Oncology Group AAML05P1 Study

Davies SM, Iannone R, Alonzo TA, Wang YC, Gerbing R, Soni S, Kolb EA, Meshinchi S, Orchard PJ, Burns LJ, Shenoy S, Leung W. A Phase 2 Trial of KIR-Mismatched Unrelated Donor Transplantation Using in Vivo T Cell Depletion with Antithymocyte Globulin in Acute Myelogenous Leukemia: Children’s Oncology Group AAML05P1 Study. Biol Blood Marrow Transplant. 2020 Apr;26(4):712-717. doi: 10.1016/j.bbmt.2019.12.723. Epub 2019 Dec 21. PubMed PMID: 31870931; PubMed Central PMCID: PMC7198330.

AML patients receiving killer immunoglobulin-like receptor (KIR) mismatched haploidentical HSCT have improved survival. COG AAML05P1 is a prospective phase 2 trial of unrelated donor (URD) HSCT in which KIR typing of donors was available to the treating physician at donor selection, aiming to determine feasibility (defined as the ability to obtain donor samples from unrelated donors and perform and return KIR data before transplant) of prospective selection of KIR mismatched donors and effect on outcomes. The study accrued 90 evaluable patients. Patients ≤ 30 years old with high risk AML at presentation or relapsed AML were eligible. After enrollment as many as 5 potential URD samples were KIR typed (including gene expression) in a central laboratory and results reported to the treating physician, who made the final donor selection. Cases were categorized as KIR matched or mismatched using different published strategies. Overall survival, disease-free survival (DFS), and relapse did not differ significantly by KIR mismatch. Acute GVHD was significantly lower in recipients of KIR mismatched stem cells (35% vs 60%, p= 0.027). We examined DFS according to time to NK-receptor recovery after HSCT. NKp44 recovery was significantly associated with KIR mismatch and with decreased DFS and increased relapse risk in multivariate Cox analysis (p= 0.006 and 0.009, respectively). We show that prospective selection of URD according to KIR type was feasible, acute GVHD was reduced, but survival did not differ using any model of KIR mismatch. The study enrolled mostly matched transplants, however, so ligand-ligand mismatch was rare and therefore sample size was insufficient to determine potential benefit according to this model. Cord blood recipients demonstrated a trend towards improved DFS with KIR mismatch, but the study was not powered to detect a difference in this small subset of patients. Our data suggest that recovery of NK receptor expression might influence DFS after HSCT.