N-803, an IL-15 superagonist complex as maintenance therapy after allogeneic donor stem cell transplant for acute myeloid leukemia or myelodysplastic syndrome; a Phase 2 trial.

Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and anti-tumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and anti-tumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n=20) (dosed 6 mcg/kg subcutaneously (SQ) at day 60 after HCT to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were in complete remission (CR). N-803 treatment was planned weekly, bi-weekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n=20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved anti-tumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (p=0.06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.