- Title
- Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG
- Creator
- Loo, Sun; Roberts, Andrew W.; Taper, John; Cull, Gavin; Tiley, Campbell; Verner, Emma; Hahn, Uwe; Hiwase, Devendra K.; Iland, Harry J.; Murphy, Nick; Ramanathan, Sundra; Reynolds, John; Anstee, Natasha S.; Ong, DM; Tiong, IS; Wall, M; Murray, M; Rawling, T; Leadbetter, J; Rowley, L; Latimer, M; Yuen, SLS; Ting, SB; Kennedy, Glen A.; Fong, CY; Morris, KL; Bajel, A; Seymour, JF; Levis, MJ; Wei, AH; He, Simon; Schwarer, Anthony P.; Enjeti, Anoop K.; D'Rozario, James; Marlton, Paula; Bilmon, Ian A.
- Relation
- Blood Vol. 142, Issue 23, p. 1960-1971
- Publisher Link
- http://dx.doi.org/10.1182/blood.2023020301
- Publisher
- American Society of Hematology
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- leukemia; sorafenib; chemotherapy; treatment outcomes; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1500023
- Identifier
- uon:54830
- Identifier
- ISSN:0006-4971
- Language
- eng
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