Quizartinib prolongs survival of newly diagnosed FLT3-ITD-mutated AML patients

OS improves when combined with standard induction and consolidation therapy, and as continuation therapy as a single agent for up to 3 years in patients.

QuANTUM-First: Studying the addition of quizartinib to induction and therapy

FLT3 is among the most common AML mutations, with FLT3-ITD mutations being associated with poor prognosis, high relapse, and inferior overall survival, and the prognosis of FLT3-TKD mutations being unclear1,2. The RATIFY study (NCT00651261) showed improved overall survival in FLT3-mutated AML patients with midostaurin, albeit with a high rate of relapse3. Quizartinib is a highly potent and selective second-generation type II FLT3 inhibitor that demonstrated a signal of clinical efficacy and a manageable safety profile in a phase 2 trial4. The QuANTUM-First trial (NCT02668653) aimed to determine if the addition of quizartinib to standard induction and post-remission consolidation therapy, followed by quizartinib continuation therapy for up to 3 years, improves survival compared with chemotherapy alone. Dr Harry Erba (Duke Cancer Institute, NC, USA) presented the results. 

The study enrolled 533 patients (18–75 years old) who were 1:1 randomised to induction therapy (cytarabine/daunorubicin) plus quizartinib or induction therapy plus placebo. In the quizartinib arm, 173 patients entered the consolidation phase (HiDAC/quizartinib and/or allo-HCT) and 116 patients thereafter continued with single-agent quizartinib. In the placebo arm, 175 patients entered the consolidation phase (HiDAC/placebo and/or allo-HCT) whereafter 92 patients continued with placebo consolidation.

Combination with intensive chemotherapy did not provide new safety signals of concern

The median overall survival (primary endpoint) was 31.9 months in the quizartinib arm versus 15.1 months in the placebo arm (HR 0.776; P=0.0324). A total of 193 patients (n=102 in the quizartinib arm, n=91 in the placebo arm) received allo-HCT. Overall survival censored for allo-HCT also numerically favoured quizartinib (HR 0.752; P=0.055). Complete remission was comparable between arms, however, the duration of complete remission was 38.6 months in the quizartinib arm versus 12.4 months in the placebo arm.

The safety of quizartinib combined with intensive chemotherapy and as continuation monotherapy was generally manageable, with no new safety signals. Discontinuation due to treatment-emergent adverse events was observed in 20.4% of patients in the quizartinib arm (versus 8.6% in the placebo arm). “These data have the potential to change the standard of care for the treatment of adult patients with newly diagnosed FLT3-ITD-mutated AML,” Dr Erba concluded.

  1. Levis M. Hematology Am Soc Hematol Educ Program. 2013;2013:220–226.
  2. Kottaridis PD, et al. Blood. 2001;98:1752–1759.
  3. Stone RM, et al. N Engl J Med. 2017;377:454–464.
  4. Takahashi T, et al. Int J Hematol. 2019;110:665–674.
  5. Erba H, 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. Abstract S100. EHA2022 Hybrid Congress, 09–12 June.