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 × 10⁶ NKAEs/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 × 10⁶ NKAEs (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 cytotoxicity <i>in vitro</i>. Infused NKAE cells were detected in bone marrow and peripheral blood after infusions. <i>Ex vivo</i> expansion 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.