Results of a phase I trial with Haploidentical mbIL‐21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML

Abstract Natural killer (NK)‐cells have potent anti‐tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 patients (median age 60 years) with refractory AML (median 5 lines of prior therapy, median bone marrow blast count of 47%) with fludarabine/cytarabine followed by 6 infusions of NK‐cells expanded from haploidentical donors using K562 feeder cells expressing membrane‐bound IL21 and 4‐1BBL. Patients received 10 6 –10 7 /kg/dose. No toxicity or graft‐versus‐host disease (GVHD) was observed and MTD was not reached. Seven patients (58.3%) responded and achieved a complete remission (CR) with/without count recovery. Median time to best response was 48 days. Five responding patients proceeded to a haploidentical transplant from the same donor. After a median follow‐up of 52 months, 1‐year overall survival (OS) for the entire group was 41.7%, better for patients who responded with CR/CRi (57.14%), and for patients who responded and underwent transplantation (60%). Persistence and expansion of donor‐derived NK‐cells were identified in patients' blood, and serum IFNγ levels rose concurrently with NK cell infusions. A higher count‐functional inhibitory KIR was associated with higher likelihood of achieving CR/CRi. In conclusion, we observed a significant response to ex vivo expanded NK‐cell administration in refractory AML patients without adverse effects.