Phase 1/2 AdaptNK adaptive CMV-induced NK-cell immunotherapy (KIR–HLA mismatch bridge-to-transplant) in R/R AML.

This Phase 1/2, open-label, multi-institution study from Masonic Cancer Center (University of Minnesota) tests an allogeneic KIR–HLA–mismatched natural killer (NK) cell infusion, “AdaptNK,” followed by a short course of subcutaneous interleukin-2 (IL-2). AdaptNK is an expanded NK-cell product enriched for “adaptive” (CMV-induced) NK cells intended to enhance anti-leukemia cytotoxicity when donor inhibitory KIRs are not engaged by the patient’s HLA ligands (i.e., KIR–HLA mismatch), potentially improving leukemia control while patients proceed to allogeneic HSCT. Patients receive lymphodepleting chemotherapy with cyclophosphamide (an alkylating DNA crosslinker) plus fludarabine (a purine analog that inhibits DNA synthesis), then a single AdaptNK infusion with IL-2 support to promote NK-cell persistence/activity. Eligible patients have relapsed/refractory AML and are restricted to HLA-C ligand groups C1/C1 or C2/C2 to operationalize donor–recipient KIR–HLA mismatch selection. Today, R/R AML is typically managed with salvage chemo or targeted agents when actionable mutations exist (e.g., FLT3/IDH inhibitors) and then transplant when feasible; this trial explores whether a biologically selected NK-cell “bridge” can deepen remission before HSCT without adding the toxicities of additional cytotoxic salvage.