Impact of hematopoietic cell transplantation and quizartinib in newly diagnosed patients with acute myeloid leukemia and FMS-like tyrosine kinase 3-internal tandem duplications in the QuANTUM-First trial.

Abstract

QuANTUM-First (NCT02668653) was a randomized phase 3 trial in newly diagnosed FLT3-ITDQpositive acute myeloid leukemia (AML) patients treated with quizartinib or placebo plus standard induction and consolidation chemotherapy and/or allogeneic hematopoietic cell transplantation (allo-HCT), followed by single-agent maintenance therapy. We evaluated the impact of allo-HCT performed in first complete remission (CR1) or composite CR1 (CRc1) on overall survival (OS), considering treatment randomization. Post-hoc extended Cox regression multivariable analyses were conducted in patients who achieved CR/CRc by the end of induction, including allo-HCT in CR1/CRc1 as a time-dependent variable to identify prognostic and predictive factors for OS. There were 297 patients with CR by the end of induction (quizartinib, n=147; placebo, n=150); of these, 157 (52.9%) underwent allo-HCT in CR1 (quizartinib, n=84; placebo, n=73). There were 368 patients with CRc by the end of induction (quizartinib, n=192; placebo, n=176); of these, 196 (53.3%) underwent allo-HCT in CRc1 (quizartinib, n=110; placebo, n=86). Multivariable analyses revealed quizartinib treatment and allo-HCT in either CR1 (hazard ratio [HR]=0.553, 95% confidence interval [CI]=0.383Q0.798, P=0.0015 and HR=0.527, 95% CI=0.349Q0.796, P=0.0023, respectively) or CRc1 (HR=0.645, 95% CI=0.470Q0.886, P=0.0068 and HR=0.557, 95% CI=0.391Q0.793, P=0.0012, respectively) as significant predictive factors for a longer OS. No new safety signals were identified. Patients who underwent protocol-specified allo-HCT in CR1/CRc1 experienced post-allo-HCTQrelated complications, mostly grade ≥2 graft-versus-host disease, as expected. This posthoc analysis further supports quizartinib and allo-HCT in CR1/CRc1 as an efficacious and well-tolerated treatment strategy for newly diagnosed FLT3-ITDQpositive AML patients fit for intensive chemotherapy.