As reported in the Journal of Clinical Oncology by Pollard et al, a subgroup of pediatric patients with KMT2A-rearranged acute myeloid leukemia (AML) in the phase III Children’s Oncology Group AAML0531 trial had improved outcomes with the addition of the CD33-targeting agent gemtuzumab ozogamicin to conventional chemotherapy.

Study Details

In the trial, 1,070 patients with de novo AML received conventional background treatment with anthracycline and cytarabine-based chemotherapy and were randomly assigned to receive gemtuzumab ozogamicin or no gemtuzumab ozogamicin in induction and intensification therapy. Patients with high-risk disease underwent hematopoietic stem cell transplant (HSCT) with an optimal donor source, and intermediate-risk patients received HSCT if a matched family donor was available. In the total population, the gemtuzumab ozogamicin group had significantly better 3-year event-free survival (53% vs 47%, P = .04) but not overall survival (69% vs 65%, P = .39). As noted by the investigators, the lack of survival benefit may have been related to increased toxicity-related mortality in patients who received postremission gemtuzumab ozogamicin (7% vs 4%, P = .09).

The current analysis assesses 5-year outcomes among the 215 patients in the trial (21% of total population) who had KMT2A-rearranged AML, including 108 in the gemtuzumab ozogamicin group and 107 in the no gemtuzumab ozogamicin group.

Key Findings

Five-year event-free survival was 48% with gemtuzumab ozogamicin vs 29% without gemtuzumab ozogamicin (P = .003); 5-year overall survival was 63% vs 53% (P = .054).

Among patients who achieved complete remission (77% of gemtuzumab ozogamicin group vs 64% of no gemtuzumab ozogamicin group), gemtuzumab ozogamicin was associated with lower 5-year relapse risk (40% vs 66%, P = .001) and improved 5-year disease-free survival (57% vs 33%, P = .002).

Overall, outcomes were poorer in patients with known high-risk KMT2A translocation partners (n = 70) vs those with known non–high-risk translocation partners (n = 107). In both subsets, gemtuzumab ozogamicin was associated with improved outcomes. Among high-risk patients, 5-year rates were 27% vs 6% for event-free survival (P = .013), 49% vs 36% for overall survival (P = .139), 29% vs 10% for disease-free survival in patients with complete remission (P = .053), and 66% vs 90% for relapse risk in patients with complete remission. Among non–high-risk patients, 5-year rates were 66% vs 42% for event-free survival (P = .017), 76% vs 67% for overall survival (P = .264), 75% vs 50% for disease-free survival (P = .025), and 22% vs 47% for recurrence risk (P = .026).

Among 30 patients who received HSCT in first complete remission, those who had received gemtuzumab ozogamicin had reduced 5-year relapse risk (28% vs 73%, P = .006) and improved disease-free survival (72% vs 27%, P = .004).

On multivariable analysis among all patients with KMT2A-rearranged AML, gemtuzumab ozogamicin vs no gemtuzumab ozogamicin was independently associated with improved 5-year event-free survival (hazard ratio [HR] = 0.52, P =.005), disease-free survival (HR = 0.47, P = .010) and risk of recurrence (HR = 0.45, P = .009). The hazard ratio for overall survival was 0.64 (P = .52).

The investigators concluded, “Gemtuzumab ozogamicin added to conventional chemotherapy improved outcomes for KMT2A-rearranged AML; consolidation with HSCT may further enhance outcomes. Future clinical trials should study CD33-targeted agents in combination with HSCT for pediatric KMT2A-rearranged AML.”

Jessica A. Pollard, MD, of Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Clinical Trials Network, National Cancer Institute, and St. Baldrick’s Foundation. For full disclosures of the study authors, visit ascopubs.org.