Single-center phase 1 trial of allogeneic natural killer cells with a bispecific innate cell engager for refractory relapsed lymphoma
Outcomes of patients with CD30-positive (CD30+) lymphomas have improved with the advent of brentuximab vedotin (BV) and, in Hodgkin lymphoma, ant-PD1 checkpoint inhibitors (CPI). However, there is a need for new therapie for patients with tumors refractory to both BC and CPI, who face dismal outcomes. The CD30/CD16A bispecific antibody AFM13 activates natural killer (NK) cells to kill CD30+ cells. A phase 1 trial at MD Anderson Cancer Center (Houston, TX) evalutated cord-blood-derived cytokine-preactivated and expanded NK cell precomplexed with AFM13 (AFM13-NK) in patients with CD30+ lymphoma refractory to BV and CPI. The trial included 42 heavily pretreated patients who received 2 to 4 cycles of lymphodepletion followed by AFM13-NK cell infusion at 3 dose levels and 3 weekly AFM13 infusions. No cytokine release syndrome, neurotoxicity, or graft-versus-host disease was observed. The highest NK dose (108 per kg) was established als the recommended phase 2 dose. The overall response and complete response rates were 92.9% and 66.7%, respectively. At a median follow-up of 20 months, the 2-year event-free and overall survival rates were 26.2% and 76.2%, respectively. Eleven patients (6 with and 5 without consolidation) remained in complete response at 14-40 months. The authors conclude that this therapy showed encouraging preliminary safety and efficacy.