Prescribing information

 

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RATIFY: International, randomised controlled Phase 3 trial of RYDAPT with standard of care* (SOC) vs. placebo plus SOC in newly diagnosed FLT3+ AML patients.1

 

 

Primary endpoint: Overall survival defined as the time from randomisation to death from any cause.1

Study design:

Study design for the randomised Phase three RATIFY trial.

 

Results: RYDAPT therapy resulted in a significant improvement in overall survival compared with placebo plus SOC.*†

Kaplan-Meier chart showing overall survival over 6 years in the RATIFY trial.

 

  • A higher proportion of patients achieved protocol-defined complete remission with RYDAPT and SOC vs. placebo and SOC1
  • More patients in the RYDAPT and SOC group underwent SCT during their first complete remission compared with placebo and SOC1

Overall survival according to subtype

  • RYDAPT with SOC increased OS vs. placebo with SOC in FLT3 positive AML1

Forest plot showing hazard ratios for overall survival

High ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively)

Overall survival in risk groups stratified by European LeukemiaNet Recommendations 20172

  • In an unplanned post-hoc exploratory analysis of a subset (n=318) of RATIFY patients with FLT3-ITD2
  • 5-year OS according to risk category were as follows:2
    • Adverse: 43% (95% CI, 0.32–0.56) RYDAPT + SOC* vs. 20% (95% CI, 0.12–0.35) with placebo + SOC*,2
    • Intermediate risk: 52% (95% CI, 0.40–0.67) with RYDAPT + SOC* vs. 34% (95% CI, 0.23–0.49) with placebo + SOC*,2
    • Favourable: 73% (95% CI, 0.60–0.89) with RYDAPT + SOC* vs. 53% (95% CI, 0.40–0.72) with placebo + SOC*,2

Risk groups characterised by European LeukemiaNet Recommendations 2017

  • Adverse (n=122): NPM1wt/FLT3-ITDhigh AML (n=92), NPM1mut/FLT3-ITDhigh AML exhibiting high-risk molecular markers (n=8), and NPM1wt/FLT3-ITDlow AML with high-risk molecular markers and/or adverse risk cytogenetics (n=22)2
  • Intermediate (n=111): NPM1mut/FLT3-ITDhigh AML (n=93) and NPM1wt/FLT3-ITDlow AML (n=18), both subgroups without the concurrent presence of the high-risk molecular markers RUNX1, ASXL1, and TP53. Also, NPM1wt/FLT3-ITDlow AML without adverse-risk cytogenetics2
  • Favourable (n=85): NPM1mut/FLT3-ITDlow AML cases, irrespective of additional high-risk gene mutation or additional chromosomal abnormalities2

Overall survival of patients, retrospectively classified according to ELN risk group and treatment2

RYDAPT: Making the opportunity for extended overall survival a reality1,3

Footnotes

AML, acute myeloid leukaemia; BID, twice daily; CI, confidence interval; CR, complete response; ELN, European LeukemiaNet; HR, hazard ratio; ITD, internal tandem duplication; IV, intravenous; OS, overall survival; q12h, every 12 hours; SCT, stem cell transplant; SOC, standard of care; TKD, tyrosine kinase domain.

* SOC: A cycle was 28 days. Chemotherapy dosing during induction was cytarabine IV, 200 mg/m2/d on Days 1–7, and daunorubicin IV, 60 mg/m2/d on Days 1–3. During consolidation, high-dose cytarabine was given at a dose of 3 g/m2/d IV q12h on Days 1, 3 and 5.

Transplantation was allowed but not specifically mandated per study protocol.

One-sided p by stratified log-rank test.

References

  1. Stone RM, Mandrekar SJ, Sanford BL, et al. N Engl J Med. 2017;377(5):454–464.
  2. Döhner K, Thiede C, Jahn N, et al. Blood. 2020; 135(5):371–380.
  3. Rydapt Summary of Product Characteristics. Novartis Pharma AG 2018.
HCP20-C026b June 2020.
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