Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Acute Myeloid Malignancies, AML, Adult, Clinical Research, Diseases, Treatment Considerations, Myeloid Malignancies, Biological Processes, Molecular biology, Study Population, Human
Methods: Multicenter, randomized, PBO-controlled, double-blinded phase II clinical trial. Patients with newly diagnosed FLT3-ITD negative AML, aged 18 to 70 years, and fit for intensive chemotherapy were centrally screened for FLT3-ITD prior to randomization. The trial was conducted in two phases: an open-label safety run-in phase exploring Cytarabine 200 mg/m2 (days 1-7), Idarubicin 12 mg/m2 (days 1-3), and Quiz 60 mg/d x 14 days to establish the dose for the randomized phase. The double-blinded phase 2:1 used randomization stratified by age (<60 vs. ≥60 years old) at diagnosis. A second identical induction cycle was allowed in case of failure to achieve CR/CRi after the first cycle. Consolidation (up to 4 cycles) consisted of high dose Cytarabine on Days 1, 3, and 5 plus Quiz or PBO for 14 days. Patients with high genetic risk or intermediate with MRD positivity were recommended for allo-SCT. A 12 cycles maintenance phase with 60 mg Quiz or PBO started after the consolidation or after allo-SCT. MRD monitoring, was performed through the PETHEMA centralized platform (PLATAFO-LMA). NPM1 and CBF patients was assessed for MRD using RT-qPCR standardized techniques, and the remaining subgroups by standardized multiparametric flow cytometry. The primary objective of QUIWI trial was to compare the event-free survival (EFS) (failure to achieve CR/CRi after 1 or 2 cycles, death in CR/CRi, or relapse, whichever occurs the first) between Quiz and PBO arms. OS was a key secondary endpoint. A blinded independent review committee (IRC) revised response assessment and European Leukemia Net (ELN) risk classification (2017 and 2022), among other critical parameters. Analyses were performed on an intent-to-treat basis.
Results: From September 2019 to November 2021, 284 Pts were enrolled in 45 Spanish PETHEMA centers, 11 of them were included in the safety run-in phase establishing 60 mg/day of Quiz for the randomized phase. 273 Pts were randomized to Quiz (n=180) or PBO (n=93). The median age was 57 y [IQR, 48 – 64 y]. Baseline pts and disease characteristics were balanced between the 2 arms (ELN 2022 risk distribution for Quiz and PBO was low 29.4% vs. 25.8%, intermediate 12.8% vs. 13.9%, and high 57.8% vs. 60.2%, p=0.8). The median follow-up was 39.4 months. Median EFS was 18.8 mo with Quiz vs. 9.9 mo with PBO (hazard ratio [HR], 0.732; 95% CI, 0.533-1.005; 2-sided P=0.053). Regarding OS, 71 out of 180 patients died in the Quiz arm, and 51 out of 93 in the PBO. Median OS was not reached with Quiz vs 29.3 mo with PBO (HR, 0.625; 95% CI, 0.436-0.897; P=0.009), and the 3-years OS was 61% with Quiz vs. 46% with PBO. Quiz benefit was observed among both <60 vs. ≥60 years old pts (HR, 0.63, P=0.067; and HR, 0.63, P=0.085, respectively), and among allo-SCT and no allo-SCT pts (HR, 0.59; P=0.16; and HR, 0.64; P=0.03, respectively). CR/CRi rate after 2 cycles was 77.2% in the Quiz arm and 76.3% in the PBO. Death during first induction cycle was 7 (4%) for Quiz and 5 (5%) for PBO. Overall, 86 (31.5%) pts received an allo-SCT after first CR/CRi, 58 (32.2%) in Quiz and 28 (30.1%) in PBO arm. Maintenance therapy started in 102 (37%) pts, 72 (40%) in Quiz and 30 (32%) in PBO arm. No new safety signals were observed among Quiz and PBO arms.
Conclusion: Our study strongly suggests that the addition of Quiz to 3+7 may prolong OS in newly diagnosed FLT3-ITD negative AML. A large global phase III randomized trial (Quantum-WT) will aim to confirm the PETHEMA-QUIWI results.
Disclosures: Montesinos: Daiichi Sankyo, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Jazzpharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Kura Oncology: Consultancy; Syndax: Consultancy; Glycomimetics: Consultancy. Tormo: SOBI: Other: Data Safety Monitoring Board; AbbVie, Gilead, Pfizer, Astellas, BMS: Honoraria; Janssen, AbbVie, Jazz: Other: Travel grant for attending meetings. Salamero: Astellas, Jazz, BMS: Consultancy; Jazz, Abbvie: Honoraria. Vidriales Vicente: F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Bena Lim, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.. Paiva: Adaptive, Amgen, Becton Dickinson, Bristol Myers Squibb/Celgene, Janssen, Merck, Novartis, Roche, Sanofi and Takeda: Honoraria; Aztra Zeneca, Bristol Myers Squibb/Celgene, EngMab, Roche, Sanofi, and Takeda: Research Funding; Bristol Myers Squibb/Celgene, Janssen, Sanofi, and Takeda: Consultancy. Martinez-Cuadron: Laboratoires Delbert: Membership on an entity's Board of Directors or advisory committees; Astellas Pharma: Consultancy; Otsuka Pharmaceutical Europe Ltd: Membership on an entity's Board of Directors or advisory committees; Servier: Other: Travel and accommodations, Speakers Bureau; Pfizer: Other: Travel and accommodations.
OffLabel Disclosure: Quizartinib is a Class III receptor tyrosine kinase (RTK) inhibitor exhibiting highly potent and selective inhibition of FMS-like tyrosine kinase 3 (FLT3). Quizartinib is currently being studied as a treatment for acute myeloid leukemia (AML)
See more of: Oral and Poster Abstracts