title: Novel treatment strategy with autologous activated and expanded natural killer cells plus anti-myeloma drugs for multiple myeloma.
abstract: This proof-of-concept single-arm open-label phase I clinical trial (NCT02481934) studied the safety and efficacy of multiple infusions of activated and expanded natural killer (NKAE) cells in combination with anti-myeloma drugs in multiple myeloma patients. It included five patients with relapsed or refractory MM who had received two to seven prior lines of therapy; NK cells were expanded for 3 weeks with K562-mb15-41BBL cells. Patients received four cycles of pharmacological treatment with two infusions of 7.5 × 106NKAEs/kg per cycle. NKAE generation, expansion, and NK monitoring was assessed using flow cytometry. Eighteen clinical-grade NKAE cell GMP-grade products were generated to obtain 627 × 106NKAEs (range: 315-919 × 106) for the first infusion and 943 × 106(range: 471-1481 × 106) for the second infusion with 90% (±7%) purity. Neutropenia grade II occurred in two patients and was related to chemotherapy. Of the five patients, four showed disease stabilization before the end of NKAE treatment, and two showed a 50% reduction in bone marrow infiltration and a long-term (>1 y) response. The NKAE cells had a highly cytotoxic phenotype and high cytotoxicityin vitro. Infused NKAE cells were detected in bone marrow and peripheral blood after infusions.Ex vivoexpansion of autologous NK cells is feasible, NKAE cells are clinically active and the multiple infusions are well tolerated in patients with relapsed or refractory myeloma.
authors.affiliation: Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; H12O-CNIO Haematological Malignancies Clinical Research Unit, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Leivas
authors.affiliation: Pediatrics Departament, Hospital la Paz , Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez-Martinez
authors.affiliation: Hematology Department, Hospital Universitario Ramón y Cajal , Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Blanchard
authors.affiliation: Hematology Department, Hospital Universitario 12 de Octubre , Madrid, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Martín-Clavero
authors.affiliation: H12O-CNIO Haematological Malignancies Clinical Research Unit, Spanish National Cancer Research Center , Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández
authors.affiliation: Hematology Department, Hospital Universitario 12 de Octubre , Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; H12O-CNIO Haematological Malignancies Clinical Research Unit, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Martinez-Lopez
keywords: Activated and expanded NK cells; cell therapy; clinical trial; immunotherapy; multiple myeloma