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

Author(s): Sun Loo1,2,3; Andrew W. Roberts1,2,3; Natasha S. Anstee2,3; Glen A. Kennedy4; Simon He5; Anthony P. Schwarer6; Anoop K. Enjeti7,8; James D’Rozario9; Paula Marlton10; Ian A. Bilmon11; John Taper12; Gavin Cull13; Campbell Tiley14; Emma Verner15; Uwe Hahn16; Devendra K. Hiwase17; Harry J. Iland18,19; Nick Murphy20; Sundra Ramanathan21; John Reynolds22; Doen Ming Ong22; Ing Soo Tiong1,22; Meaghan Wall23; Michael Murray24; Tristan Rawling25; Joanna Leadbetter26; Leesa Rowley27; Maya Latimer9; Sam Yuen7; Stephen B. Ting6; Chun Yew Fong5; Kirk Morris4; Ashish Bajel1; John F. Seymour1; Mark J. Levis28; Andrew H. Wei1,2,3,22
Source: Blood (2023) 142 (23): 1960–1971
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Sorafenib did not help in newly diagnosed AML (with FLT-ITD) patients as maintenance therapy. MRD testing can also predict survival outcome.

ABSTRACT

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.

Author Affiliations

1Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australasian; 2Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australasian; 3University of Melbourne, Parkville, VIC, Australasian; 4Royal Brisbane and Women’s Hospital, Herston, QLD, Australasian; 5Department of Clinical Haematology, Austin Health, Heidelberg, VIC, Australasian; 6Department of Haematology, Box Hill Hospital, Box Hill, VIC, Australasian; 7Calvary Mater Newcastle Hospital, Waratah, NSW, Australasian; 8University of Newcastle, Callaghan, NSW, Australasian; 9Canberra Hospital, Garran, ACT, Australasian; 10Princess Alexandra Hospital and University of Queensland, Woolloongabba, QLD, Australasian; 11Department of Haematology, Westmead Hospital, Westmead, NSW, Australasian; 12Nepean Hospital Cancer Care Centre, Kingswood, NSW, Australasian; 13Sir Charles Gairdner Hospital, University of Western Australia, Crawley, WA, Australasian; 14Gosford Hospital, Gosford, NSW, Australasian; 15Concord Repatriation General Hospital, Concord, NSW, Australasian; 16Department of Haematology, The Queen Elizabeth Hospital, Adelaide, SA, Australasian; 17Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australasian; 18Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australasian; 19University of Sydney, Camperdown, NSW, Australasian; 20Royal Hobart Hospital, Hobart, TS, Australasian; 21St George Hospital, Kogarah, NSW, Australasian; 22Department of Haematology, The Alfred Hospital and Monash University, Melbourne, VIC, Australasian; 23Murdoch Children’s Research Institute, Melbourne, VIC, Australasian; 24Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australasian; 25University of Technology Sydney, Sydney, NSW, Australasian; 26WriteSource Medical Pty Ltd, Lane Cove, NSW, Australasian; 27Australasian Leukaemia and Lymphoma Group, Richmond, VIC, Australasian; 28Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MDAustralasian

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia

Final PFS results of the ALPINE study of Zanubrutinib vs. Ibrutinib in patients with >=2L CLL/SLL. Zanubritinib was superior in terms of PFS with an HR of 0.49; at two years PFs were 78% vs. 66% in favor of Zanubritinib; improvement was seen across all subgroups. OS data is not mature yet, and that data will be interesting. Of note, the SEQUOIA study showed this drug was superior compared to Bendamustine + rituximab in the 1L setting.

Read More »