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<p>Outcomes of patients with CD30-positive (CD30<sup>+</sup>) 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<sup>+</sup> cells. Here we studied cord-blood-derived cytokine-preactivated and expanded NK cells precomplexed with AFM13 (AFM13-NK) in patients with CD30<sup>+</sup> 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<sup>6</sup>, 10<sup>7</sup> and 10<sup>8</sup> kg<sup>−1</sup>) 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: <a href="https://www.clinicaltrials.gov/study/NCT04074746">NCT04074746</a>.</p>

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Allogeneic NK cells with a bispecific innate cell engager in refractory relapsed lymphoma: a phase 1 trial

  • 期刊论文

  • 发表日期：

    2025年4月4日

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  • Yago Nieto,
  • Pinaki Banerjee,
  • Indreshpal Kaur,
  • Rafet Basar,
  • Ye Li,
  • May Daher,
  • Hind Rafei,
  • Lucila N. Kerbauy,
  • Mecit Kaplan,
  • David Marin,
  • Lori Griffin,
  • Melissa Barnett,
  • Roland Bassett,
  • Nadima Uprety,
  • Rejeena Shrestha,
  • Francia Reyes Silva,
  • Sanjida Islam,
  • Christina Ganesh,
  • Zephanie Borneo,
  • Jeremy Ramdial,
  • Alejandro Ramirez,
  • Chitra Hosing,
  • Amin Alousi,
  • Uday Popat,
  • Muzaffar Qazilbash,
  • Sairah Ahmed,
  • Swaminathan Iyer,
  • Tania P. Sainz,
  • Francisco Vega,
  • Natalie W. Fowlkes,
  • Karenza Alexis,
  • Michael Emig,
  • Andreas Harstrick,
  • Andre Overesch,
  • Elizabeth J. Shpall,
  • Katayoun Rezvani

摘要

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 (106, 107 and 108 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.