S100: 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

• DOI: 10.1097/01.hs9.0000843296.73803.85
• Publication Date: 2022-06-23T07:00:46Z
• Authors: H. Erba; P. Montesinos; R. Vrhovac; E. Patkowska; H.-J. Kim; P. Zak; P.-N. Wang; T. Mitov; J. Hanyok; L. Liu; A. Benzohra; A. Lesegretain; J. Cortes; A. Perl; M. Sekeres; H. Dombret; S. Amadori; J. Wang; M. Levis; R. Schlenk
• Keywords: Idarubicin; Mucositis

Background: Quizartinib (Quiz) is an oral, highly potent, and selective type II FLT3 inhibitor with single-agent activity in relapsed/refractory FLT3–internal tandem duplication positive (FLT3-ITD+) acute myeloid leukemia (AML). This the first report of global, randomized, double-blind, placebo (PBO)-controlled phase 3 QuANTUM-First trial (NCT02668653). Aims: aimed to determine if addition Quiz standard induction (IND) post remission (including allogeneic hematopoietic cell transplant [allo-HCT]) complete [CR1]) consolidation followed by continuation therapy for up years improved survival compared chemotherapy alone patients (pts) newly diagnosed FLT3-ITD+ AML. Methods: Pts aged 18-75 y AML were centrally screened FLT3-ITD prior initiation IND cytarabine 100 mg/m2/day (200 institutional standard) 7 days anthracycline (daunorubicin 60 or idarubicin 12 mg/m2/day) days. at 193 sites 26 countries who provided informed consent randomized (40 mg/day 8-21) PBO stratified region (North America, Europe, Asia/Other regions), age (<60 y, ≥60 y), white blood count (<40×109/L, ≥40×109/L) diagnosis. A second was allowed residual noted post-IND marrow exam. achieved CR incomplete hematologic recovery (CRi) received 4 cycles high-dose plus mg/day) and/or allo-HCT (30-60 PBO. The primary endpoint overall (OS). Results: Between September 2016 August 2019, 3468 pts screened, 539 (n=268) (n=271). median 56 (range, 20-75 y). Baseline pt disease characteristics, including variant allele frequency, balanced between 2 arms. At data cutoff (August 2021), follow-up 39.2 months 58 remained on therapy. OS significantly longer arm than (hazard ratio [HR], 0.776; 95% CI, 0.615-0.979; 2-sided P=.0324). Median 31.9 mo vs 15.1 (Figure). CR/CRi rates 71.6% 64.9%, respectively. Allo-HCT CR1 performed 157 (Quiz, 31%; PBO, 27%). When censored allo-HCT, trended (HR, 0.752; 0.562-1.008; P=0.055). Relapse-free 0.733; 0.554-0.969). Although grade ≥3 adverse events (AEs) similar across arms, neutropenia more frequent (18.1% 8.6%). Discontinuations due AEs occurred 20.4% 8.6% pts. total treatment-emergent associated a fatal outcome 11.3%; 9.7%), mostly infections. Grade 3/4 electrocardiogram QT prolonged 3.0% 1.1% Image:Summary/Conclusion: These pivotal findings show that yielded statistically significant clinically meaningful improvements adults 75 y. manageable safety profile further supports use combination therapy,