DOI: 10.1182/blood.2023020301 ISSN: 0006-4971

Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG

Sun Loo, Andrew W. Roberts, Natasha S. Anstee, Glen A. Kennedy, Simon He, Anthony P. Schwarer, Anoop K. Enjeti, James D’Rozario, Paula Marlton, Ian A. Bilmon, John Taper, Gavin Cull, Campbell Tiley, Emma Verner, Uwe Hahn, Devendra K. Hiwase, Harry J. Iland, Nick Murphy, Sundra Ramanathan, John Reynolds, Doen Ming Ong, Ing Soo Tiong, Meaghan Wall, Michael Murray, Tristan Rawling, Joanna Leadbetter, Leesa Rowley, Maya Latimer, Sam Yuen, Stephen B. Ting, Chun Yew Fong, Kirk Morris, Ashish Bajel, John F. Seymour, Mark J. Levis, Andrew H. Wei
  • Cell Biology
  • Hematology
  • Immunology
  • Biochemistry


Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years), followed by consolidation and maintenance therapy for 12 months (post-HCT excluded) in newly diagnosed patients with FLT3-ITD AML. Four patients were excluded in a modified intention-to-treat final analysis (3 not commencing therapy and 1 was FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%). With 49.1-months median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received HCT in first remission, the 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (<0.001%) after induction was associated with improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.

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