Fractionated Gemtuzumab Ozogamicin Results in Improved Survival and MRD Reduction Among Older Patients With AML

Findings from the UK NCRI AML18 Trial

Fractionated gemtuzumab ozogamicin (GO) treatment resulted in improved overall survival and a greater reduction in measurable residual disease among older patients with acute myeloid leukemia (AML), compared to single-dose gemtuzumab ozogamicin, according to findings from the UK NCRI AML18 trial published in Blood. 

“Addition of gemtuzumab ozogamicin (GO) to induction chemotherapy improves outcomes in older patients with acute myeloid leukemia (AML), but it is uncertain whether a fractionated schedule provides additional benefit to a single dose,” stated Sylvie D. Freeman, MD, University of Birmingham, Birmingham, United Kingdom, and coauthors. 

In order to assess the possibility of a fractionated gemtuzumab ozogamicin schedule providing better clinical outcomes, the study authors enrolled a total of 852 older adults, with a median age of 68 years, who had AML or high-risk myelodysplasia, in this study. The primary end point was overall survival. Patients were randomized and administered either GO on day 1 in the GO1 group, or GO on days 1 and 4 in the GO2 group. 

At a median follow-up of 50.2 months, 50%  of patients in the GO2 group who achieved a complete response had a MRD <0.1%, compared with 41% in the GO1 group. MRD reduction differed across molecular subtypes and was the largest among patients with IDH mutations.

The 5-year overall survival was 29% among patients in the GO2 group versus 24% among patients in the GO1 group (hazard ratio [HR], 0.89; P = .14). The study authors conducted a sensitivity analysis excluding patients who had adverse cytogenetics or TP53 mutations. According to this analysis, the 5-year overall survival was 33% in the GO2 group and 26% in the GO1 group. A total of 228 patients received allogeneic transplantation during the first remission. Overall survival after transplant was higher in the GO2 arm, and the survival advantage from GO2 in the sensitivity analysis was lost when patient data was censored at transplantation. 

Freeman and coauthors concluded, “GO2 was associated with a greater reduction in MRD and improved survival in older adults with non-adverse risk genetics.”

“This benefit from GO2 was dependent on allogeneic transplantation to translate the better leukemia clearance into improved survival,” they added. 

Source: 

Freeman SD, Thomas A, Thomas I, et al. Fractionated vs single-dose gemtuzumab ozogamicin with determinants of benefit in older patients with AML: the UK NCRI AML18 trial. Blood. Published online: November 16, 2023. doi: 10.1182/blood.2023020630