Nieto et al. reported favorable safety profiles and preliminary activity of cord blood-derived cytokine-pre-activated and expanded NK cells pre-complexed with AFM13 – a CD30/CD16A bispecific antibody – in 42 patients with CD30+ lymphoma refractory to both brentuximab vedotin and anti-PD-1. AFM13-NK cell infusion with subsequent infusions of AFM13 were well tolerated, without CRS, neurotoxicity, or GvHD. Donor NK cells persisted up to 3 weeks, acquired an activated and cytotoxic phenotype, and trafficked to tumor sites. At a median follow-up of 20 months, EFS and OS were 26.2% and 76.2%, respectively. Eleven patients remained in CR at 12–40 months.
Contributed by Shishir Pant
ABSTRACT: Outcomes of patients with CD30-positive (CD30(+)) lymphomas have improved with the advent of brentuximab vedotin (BV) and, in Hodgkin lymphoma, anti-PD1 checkpoint inhibitors (CPI). However, there is a need for new therapies for patients with tumors refractory to both BV and CPI, who face dismal outcomes. AFM13-a CD30/CD16A bispecific antibody-activates natural killer (NK) cells to kill CD30(+) cells. Here we studied cord-blood-derived cytokine-preactivated and expanded NK cells precomplexed with AFM13 (AFM13-NK) in patients with CD30(+) lymphoma refractory to BV and CPI. The primary endpoint of this phase_1 trial was to establish the safety and recommended phase 2 dose of AFM13-NK followed by intravenous AFM13 infusions. Secondary endpoints included the overall response rate and complete response (CR) rate, event-free survival and overall survival, and persistence of infused AFM13-NK cells. This is the final analysis of this trial; 42 heavily pretreated patients received 2 to 4 cycles of lymphodepletion followed by AFM13-NK cell infusion at 3 dose levels (10(6), 10(7) and 10(8)_kg(-1)) and 3 weekly AFM13 infusions. No cytokine release syndrome, neurotoxicity or graft-versus-host disease was observed. The highest NK dose was established as the recommended phase_2 dose. Donor NK cells peaked in blood 1_day postinfusion, persisted up to 3_weeks and trafficked to tumor sites. The overall response and CR 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 CR at 14-40 months. This therapy showed encouraging preliminary safety and efficacy. ClinicalTrials.gov Identifier: NCT04074746 .
Author Info: (1) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ynieto@mdanderson.org. (2) Department of Stem
Author Info: (1) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ynieto@mdanderson.org. (2) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (3) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (4) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (5) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (6) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (7) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (8) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (9) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (10) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (11) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (12) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (13) Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (14) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (15) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (16) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (17) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (18) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (19) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (20) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (21) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (22) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (23) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (24) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (25) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (26) Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (27) Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (28) Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (29) Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (30) Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (31) Affimed GmbH, Heidelberg, Germany. (32) Affimed GmbH, Heidelberg, Germany. (33) Affimed GmbH, Heidelberg, Germany. (34) Affimed GmbH, Heidelberg, Germany. (35) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (36) Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
