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.
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.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.