Study Compares Fractionated, Single-Dose Gemtuzumab Ozogamicin in Older Adults with AML

By Cecilia Brown - Last Updated: September 21, 2023

Fractionated gemtuzumab ozogamicin was associated with a “greater reduction” in measurable residual disease (MRD) over single-dose gemtuzumab ozogamicin in certain older adults with acute myeloid leukemia (AML), according to a recent study.

Sylvie Freeman, MD, PhD, of the University of Birmingham, and colleagues conducted the UK NCRI AML18 trial and published their findings in Blood.

They conducted the research because adding gemtuzumab ozogamicin to induction chemotherapy “improves outcomes” in older patients with AML but it is “uncertain whether a fractionated schedule provides additional benefit to a single dose,” Dr. Freeman and colleagues wrote.

The researchers randomized 852 older adults with AML or high-risk myelodysplastic syndromes to receive gemtuzumab ozogamicin on day one, or on days one and four of course-one induction.

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The complete remission (CR) rates after course-one induction were 57% in patients receiving the single dose and 63% in those receiving the fractionated dose with a median follow-up of 50.2 months (odds ratio [OR], 0.78; P=.08). Half (50%) of the patients receiving the fractionated dose achieved a CR with MRD <0.1%, which was significantly higher than the rate of 41% in the patients receiving the single dose (OR, 0.72; 33P=.027).

“This differential MRD reduction with [fractionated dosing] varied across molecular subtypes, being greatest for IDH mutations,” Dr. Freeman and colleagues wrote.

The five-year overall survival (OS) rate was 24% in patients receiving a single dose and 29% in patients receiving the fractionated dose (hazard ratio [HR], 0.89; P=.14). The researchers also conducted a sensitivity analysis that excluded patients who had adverse cytogenetics or TP53 mutations. That analysis showed the five-year OS rate was 26% in patients receiving a single dose and 33% in those receiving a fractionated dose (HR, 0.83; P=.045).

Around one-quarter (27%) of patients received an allogeneic hematopoietic stem cell transplant in their first remission. OS was “superior” for patients who received transplant and the fractionated dose (HR, 0.67; 95% CI, 0.47-0.97; P=.033), but “this benefit was lost when patients were censored at transplant,” Dr. Freeman and colleagues wrote.

“In conclusion, [fractionated gemtuzumab ozogamicin] was associated with greater reduction in MRD and improved survival in older adults with nonadverse risk genetics,” Dr. Freeman and colleagues concluded. “This benefit from [fractionated gemtuzumab ozogamicin] was dependent on [allogeneic] transplant to translate the better leukemia clearance into improved survival.”


Freeman SD, Thomas A, Thomas I, et al. Fractionated versus single dose gemtuzumab ozogamicin with determinants of benefit in older AML: UK NCRI AML18 trial. Blood. 2023. doi:10.1182/blood.2023020630

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