Adoptive immunotherapy with double-bright (CD56bright /CD16bright ) expanded natural killer cells in patients with relapsed or refractory acute myeloid leukaemia: a proof-of-concept study

Br J Haematol. 2021 Dec;195(5):710-721. doi: 10.1111/bjh.17751. Epub 2021 Sep 7.

Abstract

Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28·7%. Natural killer (NK)-cell have anti-leukaemic activity. Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56bright /CD16bright ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (106 -107 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes.

Keywords: CNS leukaemia; NK cell; R/R AML; adoptive immunotherapy.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brazil / epidemiology
  • CD56 Antigen / analysis*
  • CD56 Antigen / immunology
  • Child
  • Female
  • GPI-Linked Proteins / analysis
  • GPI-Linked Proteins / immunology
  • Graft vs Host Disease / etiology
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation*
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Proof of Concept Study
  • Receptors, IgG / analysis*
  • Receptors, IgG / immunology
  • Young Adult

Substances

  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • NCAM1 protein, human
  • Receptors, IgG