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-X
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
- Publication Type:
- Journal Article
- Citation:
- Blood, 2023, pp. blood.2023020301
- Issue Date:
- 2023-08-30
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Loo, S | |
dc.contributor.author | Roberts, AW | |
dc.contributor.author | Anstee, NS | |
dc.contributor.author | Kennedy, GA | |
dc.contributor.author | He, SZ-X | |
dc.contributor.author | Schwarer, AP | |
dc.contributor.author | Enjeti, AK | |
dc.contributor.author | D'Rozario, J | |
dc.contributor.author | Marlton, P | |
dc.contributor.author | Bilmon, I | |
dc.contributor.author | Taper, JM | |
dc.contributor.author | Cull, G | |
dc.contributor.author | Tiley, C | |
dc.contributor.author | Verner, E | |
dc.contributor.author | Hahn, U | |
dc.contributor.author | Hiwase, DK | |
dc.contributor.author | Iland, HJ | |
dc.contributor.author | Murphy, NE | |
dc.contributor.author | Ramanathan, S | |
dc.contributor.author | Reynolds, J | |
dc.contributor.author | Ong, DM | |
dc.contributor.author | Tiong, IS | |
dc.contributor.author | Wall, M | |
dc.contributor.author | Murray, M | |
dc.contributor.author |
Rawling, T https://orcid.org/0000-0002-6624-6586 |
|
dc.contributor.author | Leadbetter, J | |
dc.contributor.author | Rowley, L | |
dc.contributor.author | Latimer, M | |
dc.contributor.author | Yuen, SLS | |
dc.contributor.author | Ting, SB | |
dc.contributor.author | Fong, CY | |
dc.contributor.author | Morris, KL | |
dc.contributor.author | Bajel, A | |
dc.contributor.author | Seymour, JF | |
dc.contributor.author | Levis, MJ | |
dc.contributor.author | Wei, AH | |
dc.date.accessioned | 2023-12-05T06:01:47Z | |
dc.date.available | 2023-08-01 | |
dc.date.available | 2023-12-05T06:01:47Z | |
dc.date.issued | 2023-08-30 | |
dc.identifier.citation | Blood, 2023, pp. blood.2023020301 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.issn | 1528-0020 | |
dc.identifier.uri | http://hdl.handle.net/10453/173718 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.relation.ispartof | Blood | |
dc.relation.isbasedon | 10.1182/blood.2023020301 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine | |
dc.subject.classification | Immunology | |
dc.subject.classification | 3101 Biochemistry and cell biology | |
dc.subject.classification | 3201 Cardiovascular medicine and haematology | |
dc.subject.classification | 3213 Paediatrics | |
dc.title | Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML:a randomized, placebo-controlled study by the ALLG. | |
dc.type | Journal Article | |
utslib.location.activity | United States | |
utslib.for | 1102 Cardiorespiratory Medicine and Haematology | |
utslib.for | 1103 Clinical Sciences | |
utslib.for | 1114 Paediatrics and Reproductive Medicine | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2023-12-05T06:01:46Z | |
pubs.publication-status | Published online |
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.
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