Quizartinib Added to Chemo Boosts Overall Survival in FLT3-ITD–positive AML

The combination of quizartinib plus chemotherapy yielded better survival outcomes vs chemotherapy alone in the frontline setting of FLT3-ITD-positive acute myeloid leukemia.

In patients with previously untreated FLT3-ITD mutation–positive acute myeloid leukemia (AML), quizartinib added to induction and consolidation with standard chemotherapy and then administered as a single agent resulted in superior overall survival (OS) vs matched chemotherapy, according to results of the phase 3 QuANTUM-First trial (NCT02668653) that were presented at the 2022 European Hematology Association Congress.

At a median follow-up of 39.2 months, primary analysis for OS revealed a doubling of the median with quizartinib vs placebo at 31.9 months (95% CI, 21.0-not estimable; NE) and 15.1 months (95% CI, 13.2-26.2), respectively (HR, 0.776; 95% CI, 0.615-0.979; 2-sided P = .0324).

“The QuANTUM-First results show that adding quizartinib to standard chemotherapy significantly improved overall survival in patients with newly diagnosed FLT3-ITD-positive acute myeloid leukemia,” Harry P. Erba, MD, PhD, instructor in the Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy of Duke Cancer Institute, said in a news release. “There is great interest in the increased use of targeted therapies to improve outcomes for patients with AML, particularly those with the FLT3-ITD subtype, which is one of the most common, aggressive and difficult-to-treat.”

The study examined patients ages 18 to 75 years who presented with newly diagnosed primary or secondary AML harboring a FLT3-ITD activating mutation with an allelic ratio of 3% or greater FLT3-ITD/total FLT3 who were randomized 1:1 to chemotherapy with cytarabine and daunorubicin or idarubicin plus either quizartinib (n = 268) or matched placebo (n = 271). Induction involves up to 2 cycles of chemotherapy followed by active therapy or placebo, consolidation with up to 4 cycles of cytarabine followed by quizartinib or placebo and/or hematopoietic stem cell transplant, and up to 36 cycles of additional active therapy or placebo.

The primary end point is OS, with secondary measures of event-free survival (EFS), rate of complete remission (CR), CR composite (CRc) rate at the end of induction, safety, and pharmacokinetics.

Analysis of EFS did not yield a statistically significant benefit in either arm, with a hazard ratio of 0.916 (95% CI, 0.754-1.114; P = .2371). After controlling for patients with induction treatment failure defined as not achieving CR by day 42 of the last cycle of induction, the hazard ratio was 0.818 (95% CI, 0.669-0.999; P = .0323).

Rates of CR in the quizartinib and placebo groups were 54.9% (95% CI, 48.7%-60.9%) and 55.4% (95% CI, 49.2%-61.4%), respectively; corresponding rates of CRc were 71.6% (95% CI, 65.8%-77.0%) and 64.9% (95% CI, 58.9%-70.6%). CR with incomplete hematologic recovery occurred in 16.8% (95% CI, 12.5%-21.8%) of patients treated with quizartinib and 9.6% (95% CI, 6.4%-13.7%) of those who received placebo. Duration of CR was 38.6 months (95% CI, 21.9-NE) with quizartinib vs 12.4 months (95% CI, 8.8-22.7) with placebo. Relapse-free survival in those who achieved CR was 39.3 months and 13.6 months, respectively (HR, 0.613; 95% CI, 0.444-0.845).

No new safety signals were reported with the combination of quizartinib plus chemotherapy followed by single-agent quizartinib. The rate of grade 3 treatment-emergent adverse events (TEAEs) was similar between arms, with the exception of grade 3 neutropenia at 18.1% with the experimental regimen vs 8.6% with the control. Other grade 3 TEAEs occurring in both groups were febrile neutropenia (43.4% vs 41.0%, respectively), hypokalemia (18.9% vs 16.4%), and pneumonia (11.7% vs 12.7%).

Of note, QTcF prolongation was more common with quizartinib, with 2.3% experiencing this event and 0.8% discontinuing treatment, but ventricular arrhythmia events were uncommon. Two patients (0.8%) suffered cardiac arrest with recorded ventricular fibrillation on ECG, both with severe hypokalemia; 1 patient died as a result.

“We are proud that another one of our medicines has demonstrated a significant survival advantage, as our goal is to leverage innovative science to change the way cancer is treated,” Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, said in a news release. “Adding targeted treatment with quizartinib, a potent and selective FLT3 inhibitor, to standard chemotherapy resulted in a doubling of median overall survival in patients with newly diagnosed FLT3-ITD–positive acute myeloid leukemia compared to standard chemotherapy alone. Based on these positive QuANTUM-First results, we have initiated global regulatory filings in order to bring quizartinib to patients as quickly as possible.”


  1. Erba H, Montesinos P, Vrhovac R, et al. Quizartinib prolongs 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: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S100.
  2. Quizartinib plus chemotherapy significantly improved overall survival compared to chemotherapy in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia. News release. Daiichi Sankyo. June 11, 2022. Accessed June 13, 2022. https://yhoo.it/3NLYIW0