The addition of quizartinib to standard chemotherapy and consolidation significantly improves overall survival (OS) in adults with newly diagnosed FLT3-ITD+ acute myeloid leukemia (AML), according to final results of the phase 3 QuANTUM-First trial.
These results “have the potential to change the standard of care for the treatment of adult patients with newly diagnosed FLT3-ITD+ acute myeloid leukemia,” said study author Harry Erba, MD, PhD, of Duke Cancer Institute in Durham, North Carolina.
Dr Erba presented these results at the EHA 2022 Hybrid Congress.
QuANTUM-First (ClinicalTrials.gov Identifier: NCT02668653) included 539 patients with newly diagnosed, FLT3-ITD+ AML. All patients received standard induction with cytarabine on days 1-7 plus daunorubicin or idarubicin on days 1-3.
Patients were also randomly assigned to receive placebo (n=271) or quizartinib (n=268) at 40 mg per day on days 8-21 of induction. A second induction was allowed if residual AML was noted at the post-induction marrow exam.
Patients who achieved a complete response (CR) or CR with incomplete hematologic recovery (CRi) received consolidation with up to 4 cycles of high-dose cytarabine plus quizartinib or placebo and/or allogeneic hematopoietic stem cell transplant (allo-HSCT). This was followed by up to 36 cycles of placebo or quizartinib at 60 mg daily.
There were 173 patients in the quizartinib arm and 175 in the placebo arm who entered the consolidation phase. Protocol-specified allo-HSCT was performed in 102 patients in the quizartinib arm and 91 patients in the placebo arm. There were 116 patients in the quizartinib arm and 92 in the placebo arm who entered into the continuation phase.
At baseline, the median age was 56 years in both arms (overall range, 20-75 years), and more than 50% of patients in each arm were women. Roughly 60% of patients in each arm were White, and roughly 30% were Asian. More than 70% of patients had intermediate-risk cytogenetics, and more than half had mutated NPM1.
The primary endpoint was OS. The median OS was 31.9 months in the quizartinib arm and 15.1 months in the placebo arm (hazard ratio [HR], 0.776; 95% CI, 0.615-0.979; P =.0324).
When OS data were censored for allo-HSCT, the results were consistent with the primary analysis, Dr Erba said (HR, 0.752; 95% CI, 0.562-1.008).
Among patients who achieved a CR and received allo-HSCT in CR1, the HR for death was 0.591 (95% CI, 0.330-1.059) in the quizartinib arm. Among patients who achieved a CR but did not receive an allo-HSCT in CR1, the HR for death was 0.607 (95% CI, 0.387-0.954) in the quizartinib arm.
The CR rate was 54.9% in the quizartinib arm and 55.4% in the placebo arm. The CRi rate was 16.8% and 9.6%, respectively. The median duration of CR was 38.6 months with quizartinib and 12.4 months with placebo.
There was no improvement in event-free survival (EFS) with quizartinib when induction treatment failure was defined as no CR by day 42 of the last induction cycle (HR, 0.916; 95% CI, 0.754-1.114; P =.2371).
However, EFS was significantly longer with quizartinib when induction treatment failure was defined as no CR by the end of induction (HR, 0.818; 95% CI, 0.669-0.999; P =.0323).
Among patients who achieved a CR, the median relapse-free survival was 39.3 months with quizartinib and 13.6 months with placebo (HR, 0.613; 95% CI, 0.444-0.845). The 24-month cumulative incidence of relapse among those with a CR was 31.2% with quizartinib and 43.3% with placebo.
Nearly all patients in both arms had treatment-emergent adverse events (TEAEs). The rate of grade 3 or higher TEAEs was 92.1% with quizartinib and 89.6% with placebo.
The rate of TEAEs associated with treatment discontinuation was 20.4% in the quizartinib arm and 8.6% in the placebo arm. The rate of TEAEs associated with death was 11.3% and 9.7%, respectively.
The rate of grade 3 or higher neutropenia was higher in the quizartinib arm than in the placebo arm (18.1% and 8.6%, respectively). QT prolongation was more frequent with quizartinib than with placebo as well (13.6% vs 4.1%).
Disclosures: This research was supported by Daiichi Sankyo Inc. The presenter declared affiliations with Daiichi Sankyo, AbbVie, Agios/Servier, Astellas, ALX Oncology, Amgen, Ascentage, Bristol Myers Squibb, Celgene, Forma, Forty-Seven/Gilead, Genentech, Glycomimetics, Incyte, Immunogen, Jazz Pharmaceuticals, Kura Oncology, Macrogenics, Novartis, PTE, Takeda, and Trillium.
Erba H, Montesinos P, Vrhovac R, et al. Quizartinib prolonged survival vs placebo plus intensive induction and consolidation therapy followed by single-agent continuation in patients aged 18-75 years with newly diagnosed FLT3-ITD+ AML. Presented at EHA 2022; June 9-12, 2022. Abstract S100.