Patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) achieved rapid engraftment after receiving a CRISPR-Cas9 gene-edited donor transplant, according to a multicenter phase 1/2a trial. The approach allowed subsequent targeted maintenance therapy without prolonged blood cell toxicity.
The investigational product, tremtelectogene empogeditemcel, lacks the CD33 protein, protecting donor cells from the effects of the CD33-targeted therapy gemtuzumab ozogamicin. All 30 patients met the primary endpoint of neutrophil engraftment by Day 28, with a median time of 10 days.
Nineteen patients received gemtuzumab ozogamicin maintenance after transplant. The therapy was tolerated up to the recommended phase 2 dose, with no prolonged high-grade cytopenias. The trial published in Nature Medicine was stopped early, but the completed phase 1 component was included.
Common adverse events included cytopenias and infections. Three transplant-related deaths occurred due to renal failure, sepsis, and sinusoidal obstruction syndrome. Researchers say the approach provides a platform for post-transplant targeted therapies in high-risk patients.