CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial
CRISPR-edited donor cells without CD33 can safely engraft and tolerate targeted therapy, offering a new way to treat blood cancers after transplant.
Trem-cel is a novel CRISPR-Cas9 gene-edited allogeneic HCT product where donor cells lack CD33, shielding the graft from post-transplant gemtuzumab ozogamicin (GO) therapy targeting residual AML/MDS. In this Phase 1/2a multicenter trial (n=30 trem-cel; 19 received GO maintenance), all patients engrafted by day 28 and GO maintenance up to 2 mg/m² was tolerable, establishing proof-of-concept for CRISPR-engineered antigen deletion as a platform to enable targeted post-HCT maintenance therapy.
What the study was
- Study design
- Phase 1/2a multicenter open-label trial
- Population
- Adult AML/MDS patients with high relapse risk undergoing allogeneic HCT
- Sample size
- 30
- Category
- Treatment Innovation
- Maturity
- Exploratory
- Journal
- Nature Medicine
Why it surfaced
First-in-class CRISPR antigen-deletion strategy for allogeneic HCT enabling post-transplant targeted maintenance without donor graft toxicity. Phase 1/2a multicenter trial in high-risk AML/MDS; all 30 patients engrafted, GO maintenance tolerated. Trial stopped early; 3/30 TRM. Nat Med publication. Despite early trial termination and small n, this is a conceptually transformative platform approach for post-HCT relapse prevention.
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