For treatment-eligible patients with newly
diagnosed FLT3-ITD+ AML
Start and stay with VANFLYTA—The only FLT3 inhibitor indicated for INDUCTION,
CONSOLIDATION, AND MAINTENANCE1-3*
*Please see Full Indication,
including
Limitations of Use, below.
QuANTUM-First is the only pivotal trial to specifically study FLT3-ITD+ AML patients through induction, consolidation, and maintenance1-3*
- The efficacy and safety of VANFLYTA vs placebo were studied over a 5-year period in a Phase 3, randomized, double-blind, placebo-controlled, multicenter global study of patients with newly diagnosed FLT3-ITD+ AML1,4
VANFLYTA is indicated across all 3 treatment phases: induction, consolidation, and maintenance1,4,5*
- Patients were stratified by age (<60 vs ≥60 years), white blood cell count at diagnosis (<40x109/L vs ≥40x109/L), and region (North America, Europe vs Asia, other regions)1
Standard chemotherapy included cytarabine- and anthracycline-based induction (either daunorubicin or idarubicin) and consolidation regimens. Eligible patients, including those who underwent allogeneic HSCT, continued with single agent VANFLYTA or standard chemotherapy. There was no re-randomization at the start of post-consolidation therapy.1,4
- Among the patients who entered maintenance, 64% completed at least 12 cycles, 36% completed at least 24 cycles, and 16% completed all 36 planned cycles of maintenance*
- 29% (157/539) of the patients underwent HSCT in first CR
A second course of induction was administered to 20% of the patients; 65% initiated at least 1 cycle of consolidation; and 39% initiated maintenance treatment with VANFLYTA.1*
*Limitations of Use: VANFLYTA is not indicated as maintenance monotherapy following allogeneic HSCT; improvement in overall survival with VANFLYTA in this setting has not been demonstrated.
†Patients received 35.4 mg orally once daily on Days 8-21 of 7+3 (cytarabine [100 or 200 mg/m2/day] on Days 1-7 plus daunorubicin [60 mg/m2/day] or idarubicin [12 mg/m2/day] on Days 1-3), and on Days 8-21 or 6-19 of an optional second induction (7+3 or 5+2 [5 days cytarabine plus 2 days daunorubicin or idarubicin], respectively). During Cycle 2 of the Induction phase, VANFLYTA or placebo started on Day 8 or Day 6, depending on the chemotherapy regimen selected (7+3 or 5+2, respectively).1
‡Randomization may be performed later, between Days 8-10, to address clinical concerns (eg, electrolyte abnormalities or QT prolongation).5
§Consolidation chemotherapy consisted of 35.4 mg orally once daily on Days 6-19 of high-dose cytarabine (1.5 to 3 g/m2 every 12 hours on Days 1, 3, and 5) for up to 4 cycles.1
VANFLYTA was studied in the largest and longest trial of patients with newly diagnosed FLT3-ITD+ AML1,4
BASELINE PATIENT CHARACTERISTICS4
- Studied in a wide range of ages, up to 75 years with 40% of patients over 60 years4
- Of the 539 randomized patients1:
- The majority of the patients (72%) had intermediate-risk cytogenetics at baseline
- FLT3-ITD VAF was 3-25% in 36% of patients, >25-50% in 52% of patients, and >50% in 12% of patients
- NPM1 mutations were identified in 52% of patients
*Three patients in the ITT set were randomized but not treated in each arm.4
†One patient in the placebo group was missing an ECOG status.4
‡Favorable: inv(16), t(16;16), t(8;21), or t(15;17); intermediate: normal, 8, 6, or −Y; unfavorable: deI(5q), −5, del(7q), −7, or complex karyotype.4
In patients with newly diagnosed FLT3-ITD+ AML treated with VANFLYTA plus standard chemotherapy
VANFLYTA provided superior overall survival vs standard chemotherapy alone1,4
The study demonstrated a statistically significant improvement in OS for the VANFLYTA arm.1,4
PRIMARY ENDPOINT: OVERALL SURVIVAL IN VANFLYTA1,4
REDUCTION IN THE RISK OF
DEATH WITH VANFLYTA + STANDARD
CHEMOTHERAPY
vs placebo + standard chemotherapy
HR: 0.78†
(95% CI: 0.62-0.98); P=0.03241‡
- In an exploratory subgroup analysis of patients (89/208) who received maintenance therapy with VANFLYTA or placebo following consolidation chemotherapy, the OS HR was 0.40 (95% CI: 0.19-0.84)1
- Of 57% of patients (119/208) who received maintenance therapy with VANFLYTA or placebo following HSCT, the OS HR was 1.62 (95% CI: 0.62-4.22)1*
*Limitations of Use: VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.
†Hazard ratio is based on stratified Cox proportional hazard model stratified by the stratified factors used in randomization.4
‡P value was calculated using a stratified log-rank test.4
The primary analysis was conducted after a minimum follow-up of 24 months after the randomization of the last patient.1
VANFLYTA was studied for complete remission and composite complete remission1,5
SECONDARY ENDPOINTS1,5
Primary EFS analysis (with ITF defined as not achieving CR by Day 42 from the start of the last induction cycle) did not show a statistical significance between the 2 study arms (HR=0.916 [95% CI=0.75-1.11]).4
- Since EFS was not statistically significant, formal hierarchical testing on other secondary endpoints, including CR and CRc, was stopped; their results are provided descriptively5
*CRc is equal to complete remission (CR) + CR with incomplete neutrophil or platelet recovery (CRi) after induction.5
VANFLYTA duration of complete remission vs standard chemotherapy alone1
EXPLORATORY ENDPOINT: DURATION OF COMPLETE REMISSION1*
*By independent review committee.7
VANFLYTA RFS rates in patients with a complete response vs standard chemotherapy alone4
EXPLORATORY ENDPOINT: RELAPSE-FREE SURVIVAL7*
- 39% reduction in the risk of relapse or death vs placebo
+ standard chemotherapy; HR: 0.61 (95% CI:
0.44-0.8)4
- Analysis on RFS, which was a prespecified exploratory outcome, was not powered to detect a difference in treatment effect between the 2 arms. Cautious interpretation is recommended, and no conclusions can be drawn from this data
*In patients who achieved CR by end of induction by IRC.4
VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected by an FDA-approved test.
Limitations of Use: VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.
AML=acute myeloid leukemia; CI=confidence interval; CRc=composite complete remission; CR=complete remission; DoCR=duration of complete remission; ECOG=Eastern Cooperative Oncology Group; EFS=event-free survival; FLT3=FMS (feline McDonough sarcoma)–like tyrosine kinase 3; HR=hazard ratio; HiDAC=high-dose cytarabine; HSCT=hematopoietic stem cell transplantation; IRC=independent review committee; ITD=internal tandem duplication; ITF=induction treatment failure; ITT=intention-to-treat; mRFS=median relapse-free survival; NE=not estimable; NPM1=nucleophosmin; OS=overall survival; RFS=relapse-free survival; VAF=variant allelic frequency.
1. VANFLYTA [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc; 2024. 2. XOSPATA [package insert]. Northbrook, IL: Astellas Pharma US, Inc; 2022. 3. RYDAPT [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2023. 4. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online: April 25, 2023. doi:10.1016/S0140-6736(23)00464-6 5. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Supplementary appendix. Lancet. Published online: April 25, 2023. doi:10.1016/S0140-6736(23)00464-6
