Nilotinib with or without cytarabine for Philadelphia-positive acute lymphoblastic leukemia.

Details

Serval ID
serval:BIB_89C66CC22232
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nilotinib with or without cytarabine for Philadelphia-positive acute lymphoblastic leukemia.
Journal
Blood
Author(s)
Chalandon Y., Rousselot P., Chevret S., Cayuela J.M., Kim R., Huguet F., Chevallier P., Graux C., Thiebaut-Bertrand A., Chantepie S., Thomas X., Vincent L., Berthon C., Hicheri Y., Raffoux E., Escoffre-Barbe M., Plantier I., Joris M., Turlure P., Pasquier F., Belhabri A., Guepin G.R., Blum S., Gregor M., Lafage-Pochitaloff M., Quessada J., Lhéritier V., Clappier E., Boissel N., Dombret H.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
06/06/2024
Peer-reviewed
Oui
Volume
143
Number
23
Pages
2363-2372
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Multicenter Study
Publication Status: ppublish
Abstract
We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace hyper-CVAD (cyclophosphamide-vincristine-doxorubicin [Adriamycin]-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation). All patients were eligible for allogeneic stem cell transplant (SCT), whereas those in MMR could receive autologous SCT, followed by 2-year imatinib maintenance in both cases. After the enrollment of 156 of 265 planed patients, the data and safety monitoring board decided to hold the randomization because of an excess of relapse in the investigational arm. Among the 155 evaluable patients, 76 received Ara-C during consolidation (arm A) and 79 did not (arm B). Overall, 133 patients (85%) underwent SCT, 93 allogeneic and 40 autologous. The noninferiority end point regarding MMR was reached with 71.1% (arm A) and 77.2% (arm B) of patients reaching MMR. However, the 4-year cumulative incidence of relapse was higher in arm B compared with arm A (31.3% [95% confidence interval {CI}, 21.1%-41.9%] vs 13.2% [95% CI, 6.7%-21.9%]; P = .017), which translated to a lower relapse-free survival. With a median follow-up of 3.8 years, 4-year overall survival was 79.0% (95% CI, 70.6%-89.3%) in arm A vs 73.4% (95% CI, 63.9%-84.4%) in arm B (P = .35). Despite a noninferior rate of MMR, more relapses were observed when ARA-C was omitted without impact on survival. ClinicalTrials.gov ID, NCT02611492.
Keywords
Humans, Cytarabine/administration & dosage, Cytarabine/therapeutic use, Female, Male, Adult, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Pyrimidines/therapeutic use, Pyrimidines/administration & dosage, Aged, Young Adult, Adolescent, Fusion Proteins, bcr-abl/genetics, Hematopoietic Stem Cell Transplantation
Pubmed
Create date
11/03/2024 12:22
Last modification date
15/06/2024 7:03
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