Combining quizartinib with intensive chemotherapy for older patients with newly diagnosed AML: results of the UK NCRI AML18 trial.

In 30 seconds

The multicentre randomised UK NCRI AML18 trial evaluated quizartinib after intensive chemotherapy, with or without maintenance, in patients older than 60 years with newly diagnosed AML or high-risk myelodysplastic syndrome, irrespective of FLT3 status. Among 463 participants (median age 68 years), quizartinib did not significantly improve overall survival in the full population and increased non-relapse mortality. In a pre-planned subgroup, patients with FLT3-mutated disease had improved overall survival with quizartinib (hazard ratio 0.59; 95% confidence interval, 0.37-0.93; P = .024), associated with reduced relapse risk.

Key findings

• In the population unselected for FLT3 status, quizartinib did not significantly improve overall survival and was associated with increased non-relapse mortality.
• For patients with FLT3 mutations, quizartinib improved overall survival (hazard ratio 0.59; 95% confidence interval, 0.37-0.93; P = .024), with reduced relapse risk.
• Patients with FLT3-wild-type disease had no survival benefit or reduction in relapse risk.
• Quizartinib did not significantly affect hematologic count recovery or hospital length of stay; febrile neutropenia was the most observed grade 3/4 adverse event.

Why it matters

The findings indicate that FLT3 mutation status may be important when assessing quizartinib alongside intensive chemotherapy in older patients. The absence of an overall survival benefit in the unselected population, together with increased non-relapse mortality, underscores the need to interpret the subgroup benefit in the context of treatment harms and the trial’s specific treatment schedule.

What to keep in mind

The primary overall-survival analysis in the population unselected for FLT3 status showed no significant benefit; the positive result was from a pre-planned subgroup analysis.