CRISPR-Edited Cell Transplant with GO Maintenance Shows Promise in AML Trial
A first-in-human phase 1/2 clinical trial published in Nature Medicine demonstrates the safety and efficacy of tremtelectogene empogeditemcel (trem-cel), a CRISPR-Cas9 gene-edited allogeneic hematopoietic cell transplant lacking CD33, combined with gemtuzumab ozogamicin (GO) maintenance for high-risk acute myeloid leukemia (AML). The study involved 30 adult patients who received trem-cel after myeloablative conditioning. All participants achieved primary neutrophil engraftment by day 28, with a median time of 10 days, indicating robust graft function. Nineteen patients subsequently received GO maintenance therapy. The treatment was well-tolerated, with no prolonged high-grade cytopenias observed, addressing a major limitation of post-transplant maintenance strategies. While three transplant-related deaths occurred due to renal failure, sepsis, and sinusoidal obstruction syndrome, the trial successfully demonstrated that CD33 deletion shields donor cells from GO toxicity. This approach allows for targeted elimination of residual CD33-positive leukemia cells without harming the transplanted graft. The trial was stopped early after completing the phase 1 portion, marking a significant advancement in using gene editing to enhance the effectiveness of antibody-drug conjugates in preventing AML relapse.
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CRISPR-Edited Cell Transplant with GO Maintenance Shows Promise in AML Trial
A first-in-human phase 1/2 clinical trial published in Nature Medicine demonstrates the safety and efficacy of tremtelectogene empogeditemcel (trem-cel), a CRISPR-Cas9 gene-edited allogeneic hematopoietic cell transplant lacking CD33, combined with gemtuzumab ozogamicin (GO) maintenance for high-risk acute myeloid leukemia (AML). The study involved 30 adult patients who received trem-cel after myeloablative conditioning. All participants achieved primary neutrophil engraftment by day 28, with a median time of 10 days, indicating robust graft function. Nineteen patients subsequently received GO maintenance therapy. The treatment was well-tolerated, with no prolonged high-grade cytopenias observed, addressing a major limitation of post-transplant maintenance strategies. While three transplant-related deaths occurred due to renal failure, sepsis, and sinusoidal obstruction syndrome, the trial successfully demonstrated that CD33 deletion shields donor cells from GO toxicity. This approach allows for targeted elimination of residual CD33-positive leukemia cells without harming the transplanted graft. The trial was stopped early after completing the phase 1 portion, marking a significant advancement in using gene editing to enhance the effectiveness of antibody-drug conjugates in preventing AML relapse.
Nature Medicine