Hematology ·
Quizartinib improved survival in older patients with FLT3-mutated AML in AML18
In the randomized UK NCRI AML18 trial, 463 patients older than 60 years with newly diagnosed AML or high-risk myelodysplastic syndrome received intensive chemotherapy with or without quizartinib. Quizartinib did not improve overall survival in the full population, but a prespecified subgroup analysis found improved survival among patients with FLT3-mutated AML; non-relapse mortality increased with quizartinib.
- No overall survival benefit in the full trial population.
- FLT3-mutated subgroup had improved survival with quizartinib.
- Non-relapse mortality increased with quizartinib.
- No survival benefit was seen in FLT3-wild-type disease.
The UK NCRI AML18 trial randomized 463 patients aged over 60 years (median age, 68) with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to intensive chemotherapy with or without quizartinib. Quizartinib was given after chemotherapy courses 2 and 3; patients assigned to it were also randomized to 12 additional maintenance courses or no further treatment. Median follow-up was 76 months. The primary endpoint was overall survival (OS), assessed regardless of FLT3 mutation status.
Quizartinib did not significantly improve OS in the overall trial population, and non-relapse mortality was significantly higher. In a prespecified subgroup analysis, patients with FLT3-mutated AML who received quizartinib had better OS than those who did not (hazard ratio 0.59; 95% CI 0.37–0.93; P=.024), attributed to reduced relapse risk. The reported benefit was greater with the shorter quizartinib course. Patients with FLT3-wild-type disease had no survival benefit or reduction in relapse risk.
There were no significant differences in time to blood-count recovery or hospital stay; febrile neutropenia was the most frequently observed grade 3/4 adverse event. The findings support a potential benefit in older patients with FLT3-mutated AML, but not in the unselected population. Interpretation should account for the increased non-relapse mortality and the subgroup-specific nature of the survival result.
In practice
For adults older than 60 years with newly diagnosed FLT3-mutated AML receiving intensive chemotherapy, AML18 found improved overall survival with quizartinib in a prespecified subgroup (HR 0.59; 95% CI 0.37–0.93). The overall trial population did not benefit, patients with FLT3-wild-type disease had no survival benefit, and non-relapse mortality increased. These subgroup findings may inform consideration of quizartinib in this setting, but they do not support use across an unselected older AML population; the supplied abstract does not provide further safety or subgroup detail.
AI-generated clinical interpretation · Not editor-reviewed
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Blood: Combining quizartinib with intensive chemotherapy for older patients with newly diagnosed AML: results of the UK NCRI AML18 trial ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.