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The prognosis of non-Hodgkin lymphoma (NHL) remains poor, with an unmet need for novel therapies. MG4101, an ex vivo-expanded allogeneic natural killer cell, can enhance rituximab antibody-dependent cytotoxicity in relapsed/refractory B-cell non-Hodgkin lymphoma (r/rNHL).To assess the safety and efficacy of MG4101 plus rituximab for patients with r/rNHL.Patients received escalating doses of intravenous MG4101 plus rituximab every 2 weeks. Interleukin-2 was administered subcutaneously after MG4101 treatment. Fludarabine plus cyclophosphamide was administered intravenously before rituximab treatment in cycles 1, 3, and 5. A 3+3 design was used to determine the maximum tolerated dose (MTD) and maximum feasible dose (MFD). Assessments were performed over a six-cycle period, with an extended maintenance period of up to eight cycles. Nine patients received three different doses of MG4101 and rituximab. MTD could not be determined because of the absence of dose-limiting toxicity.Treatment-related adverse events, mostly grade 1 or 2, occurred in 89% of patients. Only one patient experienced grade 1 cytokine release syndrome. MG4101 persisted for at least 7 days in seven patients. Four patients achieved a partial response, and one attained a complete response, yielding a 55.6% response rate. Two patients showed prolonged responses and low exhaustion marker levels in T-cells.For allogeneic natural killer cell therapy, strategies including the use of the high-affinity hFcγRIIIaV158 variant of the KIR B/x haplotype with lymphodepleting chemotherapy could be promising options for improving clinical efficacy in the antibody combination therapeutic setting as an off-the-shelf product. MG4101 plus rituximab presented a favorable safety profile and overall response rate in patients with r/rNHL. |
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