BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the "GRUPPO TRIVENETO LMC".
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
16
07
2022
received:
28
05
2022
accepted:
02
08
2022
pubmed:
9
10
2022
medline:
25
2
2023
entrez:
8
10
2022
Statut:
ppublish
Résumé
We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087.
Identifiants
pubmed: 36208021
doi: 10.1002/cam4.5158
pmc: PMC9939132
doi:
Substances chimiques
Imatinib Mesylate
8A1O1M485B
Fusion Proteins, bcr-abl
EC 2.7.10.2
Protein Kinase Inhibitors
0
Types de publication
Letter
Langues
eng
Sous-ensembles de citation
IM
Pagination
3180-3184Informations de copyright
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Baccarani M, Abruzzese E, Accurso V, et al. Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP. Blood Adv. 2019;3:4280-4290.
Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966-984.
Breccia M, Efficace F, Colafigli G, et al. Tyrosine kinase inhibitor discontinuation in the management of chronic myeloid leukemia: a critical review of the current practice. Expert Rev Hematol. 2020;13:1311-1318.
Etienne G, Guilhot J, Rea D, et al. Long-term follow-up of the French stop imatinib (STIM1) study in patients with chronic myeloid leukemia. J Clin Oncol. 2017;35:298-305.
Campiotti L, Suter MB, Guasti L, et al. Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: a systematic review and a meta-analysis. Eur J Cancer. 2017;77:48-56.
Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19:747-757.
Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129:846-854.
Sharf G, Marin C, Bradley JA, et al. Treatment-free remission in chronic myeloid leukemia: the patient perspective and areas of unmet needs. Leukemia. 2020;34:2102-2112.
Takahaschi N, Kyo T, Maeda T, et al. Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia. Haematologica. 2012;97:903-906.
Lee S-E, Choi SY, Song H-Y, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016;101:717-723.
Clark RE, Polydoros F, Apperley JF, et al. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY); a non-randomised, phase 2 trial. Lancet Hematol. 2019;6:e375-e383.
Chamoun K, Kantarjian H, Atallah R, et al. Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience. J Hematol Oncol. 2019;12:1.
Kim DDH, Novitzky-Basso IN, Kim T, et al. BCR::ABL1 transcript doubling time after imatinib discontinuation for treatment-free remission in chronic myeloid leukemia in chronic phase: predictor for treatment-free remission failure. Blood. 2020;136(supp 1):40-41. Abstract #1234.
Mori S, Vagge E, le Coutre P, et al. Age and dPCR can predict relapse in CML patients who discontinued imatinib: the ISAV study. Am J Hematol. 2015;90:910-914.
Colafigli G, Scalzulli F, Porrazzo M, et al. Digital droplet PCR at the time of TKI discontinuation in chroni-phase chronic myeloid leukemia patients is predictive of treatment-free remission outcome. Hematol Oncol. 2019;37:652-654.