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

Loo, S; Roberts, AW; Anstee, NS; Kennedy, GA; He, SZ; Schwarer, AP; Enjeti, AK; D&#39;Rozario, J; Marlton, P; Bilmon, I; Taper, JM; Cull, G; Tiley, C; Verner, E; Hahn, U; Hiwase, DK; Iland, HJ; Murphy, NE; Ramanathan, S; Reynolds, J; Ong, DM; Tiong, IS; Wall, M; Murray, M; Rawling, T; Leadbetter, J; Rowley, L; Latimer, M; Yuen, SLS; Ting, SB; Fong, CY; Morris, KL; Bajel, A; Seymour, JF; Levis, MJ; Wei, AH

Author(s): Loo, S; Roberts, AW; Anstee, NS; Kennedy, GA; He, SZ; Schwarer, AP; Enjeti, AK; D'Rozario, J; Marlton, P; Bilmon, I; Taper, JM; Cull, G; Tiley, C; Verner, E; Hahn, U; Hiwase, DK; Iland, HJ; Murphy, NE; Ramanathan, S; Reynolds, J; Ong, DM; Tiong, IS; Wall, M; Murray, M; Rawling, T; Leadbetter, J; Rowley, L; Latimer, M; Yuen, SLS; Ting, SB; Fong, CY; Morris, KL; Bajel, A; Seymour, JF; Levis, MJ; Wei, AH;
Details: Publication Year 2023-08-30,Volume 142,Issue #23,Page 1960-1971
Journal Title: Blood
Abstract: Sorafenib maintenance improves outcome after hematopoietic cell transplant (HCT) for patients with 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 18-65 years (2:1) to sorafenib vs placebo (days 4-10) combined with intensive induction; idarubicin 12mg/m2 days 1-3 plus cytarabine 1.5g/m2 twice daily on days 1,3,5,7 (18-55 years) or 100mg/m2 days 1-7 (56-65 years), consolidation therapy, followed by maintenance treatment for 12 months (post-HCT excluded) in newly diagnosed FLT3-ITD AML. Four patients were excluded from modified intention-to-treat final analysis (3 not dosed and 1 later found to be FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery (CR/CRi) were high in both arms (sorafenib 78%/9%, placebo 70%/24%). With 49.1 months median follow-up, the primary endpoint 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=0.61). 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 transplanted in first remission, 2-year OS was 84% and 67% in the sorafenib and placebo arms, respectively (HR 0.45;95% CI 0.18-1.12, p=0.08). In exploratory analyses, FLT3-ITD measurable residual disease negative status (<0.001%) post-induction was associated with improved 2-year OS (83% vs 60%) (HR 0.4;95% CI 0.17-0.93, p=0.028). In conclusion, routine use of pre-transplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.
Publisher: ASH
Keywords: Humans; Sorafenib; fms-Like Tyrosine Kinase 3/genetics; *Hematopoietic Stem Cell Transplantation; Retrospective Studies; *Leukemia, Myeloid, Acute/drug therapy/genetics
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 37647654
Publisher's Version: https://doi.org/10.1182/blood.2023020301
Open Access at Publisher's Site: https://doi.org/10.1182/blood.2023020301
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-09-07 09:17:10

Last Modified: 2023-12-13 10:19:49