I 期研究：体外扩增同种异体 NK 细胞（MG4101）联合利妥昔单抗治疗复发/难治性 B 细胞非霍奇金淋巴瘤的安全性和有效性

The prognosis of non-Hodgkin lymphoma (NHL) remains poor, with an unmet need for novel therapies. MG4101, an ex vivo-expanded allogeneic natural killer (NK) cell, can enhance rituximab antibody-dependent cytotoxicity in relapsed/refractory (r/r) B cell non-Hodgkin lymphoma.

This study assessed the safety and efficacy of MG4101 plus rituximab for patients with r/r NHL. Patients received escalating doses of i. v. MG4101 plus rituximab every 2 weeks. IL-2 was administered s. c. after MG4101 treatment. Fludarabine plus cyclophosphamide was administered i. v. 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. Assessments were performed over a 6-cycle period, with an extended maintenance period of up to 8 cycles. Nine patients received 3 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 1 patient experienced grade 1 cytokine release syndrome. MG4101 persisted for at least 7 days in 7 patients. Four patients achieved a partial response and 1 patient attained a complete response, for an overall response rate of 55. 6%. Two patients showed prolonged responses and low exhaustion marker levels in T cells.

For allogeneic NK cell therapy, strategies including the use of the high-affinity hFc RIIIaV158 variant of the KIR B/x haplotype with lymphodepleting chemotherapy may 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/r NHL.