Trem-cel enables repeated post-HCT maintenance dosing of gemtuzumab ozogamicin in patients with high-risk AML
Preliminary results of a phase 1/2 multicenter trial showed that tremtelectogene empogeditemcel (trem-cel) enabled posthematopoietic 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.
The results were presented at the 2024 American Society of Hematology Annual Meeting and Exposition in San Diego, California, by John DiPersio, MD, PhD, of the Division of Oncology at Washington University School of Medicine in Saint Louis, Missouri.
Trem-cel (formerly VOR33), a CD33-deleted allograft, is a hematopoietic stem and progenitor cell product manufactured from CD34-positive cells from a matched donor and CRISPR/Cas9 gene-edited to delete CD33. It was developed to shield normal hematopoietic cells from CD33-directed therapies and allow exclusive targeting of residual CD33-positive leukemia.
The purpose of the ongoing trial is to establish the safety of using trem-cel as an allograft followed by maintenance therapy with GO, an anti-CD33 antibody-drug conjugate, for patients with CD33-positive AML or myelodysplastic syndromes (MDS) who are at high risk of relapse and undergoing HSCT.
In the results presented, 18 patients had received trem-cel, all of whom achieved primary neutrophil engraftment and platelet recovery excluding one patient with antiplatelet antibodies, and 10 of the 18 patients received maintenance GO.
The results showed that trem-cel rapidly engrafted and sustained hematopoiesis with persistent absence of CD33 in the myeloid compartment, and that CD33-deleted hematopoietic cells showed protection from the prolonged deep cytopenias associated with GO. No episodes of grade 4 neutropenia were observed and only a single episode of grade 4 thrombocytopenia was reported in 40 GO cycles administered.
Given that GO exposures correlate with higher doses in the standard relapsed or refractory AML population, trem-cel supports an increased therapeutic window for GO, according to the researchers.
“These data support safe and effective administration of GO after trem-cel HCT, enabling repeated maintenance dosing intended to reduce risk of relapse,” the authors wrote.
Reference
DiPersio J, Koehne G, Shah N. 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). Abstract #2873. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10; San Diego, California.
