Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial

Richard A. Larson*, Sumithra J. Mandrekar, Lucas J. Huebner, Ben L. Sanford, Kristina Laumann, Susan Geyer, Clara D. Bloomfield, Christian Thiede, Thomas W. Prior, Konstanze Döhner, Guido Marcucci, Maria Teresa Voso, Rebecca B. Klisovic, Ilene Galinsky, Andrew H. Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, Theo de Witte, Dietger NiederwieserFrederick R. Appelbaum, Bruno C. Medeiros, Martin S. Tallman, Jürgen Krauter, Richard F. Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Insa Gathmann, Hartmut Döhner, Richard M. Stone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54–0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR.

Original languageEnglish (US)
Pages (from-to)2539-2551
Number of pages13
Issue number9
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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