A CD33-Deleted Allograft (Trem-cel) Enables Post-Hematopoietic Cell Transplant (HCT) Maintenance Dosing of Gemtuzumab Ozogamicin (GO) with Therapeutic Levels of Drug Exposure and Low Hematologic and Hepatic Toxicity in Patients with High-Risk Acute Myeloid Leukemia (AML)

作者：John F. DiPersio, Guenther Koehne, Nirali N. Shah, Léa Bernard, Hyung C. Suh, Divya Koura, Miguel‐Angel Perales, Roni Tamari, Muhammad Umair Mushtaq, Joseph Maakaron, Michael R. Loken, Darren Stanizzi, Melissa M. Lee‐Sundlov, Sanjana Thosar, Sharon L. Hyzy, Glen Raffel, Brenda Cooper · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-205641 · 被引用次数：5 · 研究领域：Chronic Myeloid Leukemia Treatments、Acute Myeloid Leukemia Research、Chronic Lymphocytic Leukemia Research

Background: Relapse is the leading cause of death for patients undergoing allogeneic HCT for AML. Strategies to reduce relapse including leukemia-directed maintenance therapies post-HCT have been largely ineffective. GO (MylotargTM) is an anti-CD33 antibody-drug conjugate approved for use in AML, but its use has been limited by hepatotoxicity and on-target, off-tumor hematopoietic toxicity toward CD33+ normal blood cells leading to severe cytopenias, especially post-HCT. Tremtelectogene empogeditemcel (trem-cel; formerly VOR33) is a hematopoietic stem and progenitor cell product manufactured from CD34+ cells from a matched donor and CRISPR/Cas9 gene-edited to delete CD33. Trem-cel was developed to shield normal hematopoietic cells from CD33-directed therapies and allow exclusive targeting of residual CD33+ leukemia. Methods: VBP101 (NCT04849910) is a Phase 1/2 multicenter trial to establish the safety of using trem-cel as an allograft followed by GO maintenance therapy for patients with CD33+ AML or MDS who are at high risk of relapse and undergoing HCT. Patients (18-70 y) must have CD33+ AML/MDS with high-risk features for relapse, such as adverse-risk cytogenetics or measurable residual disease, and an 8/8 HLA-matched related or unrelated donor. Trem-cel is manufactured from donor CD34+ cells isolated from G-CSF/Plerixafor-mobilized peripheral blood. Patients undergo busulfan- or TBI-based myeloablative conditioning with rATG prior to HCT with trem-cel. After ~60 days post-...