Dasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study).
chronic myeloid leukaemia
clinical trial
deep molecular response
pegylated-interferon
tyrosine kinase inhibitor
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
04
09
2022
received:
13
05
2022
accepted:
16
09
2022
pubmed:
11
10
2022
medline:
14
1
2023
entrez:
10
10
2022
Statut:
ppublish
Résumé
Superior rates of deep molecular response (DMR) have been reported with the combination of tyrosine kinase inhibitors and pegylated-interferon-alpha (Peg-IFN) in patients with newly diagnosed chronic phase-chronic myeloid leukaemia (CP-CML). In this setting, this study investigated the efficacy and safety of dasatinib combined to Peg-IFN-α2b (Dasa-PegIFN, NCT01872442). A total of 79 patients (age ≤65 years) started dasatinib; 61 were eligible for Peg-IFNα-2b add-on therapy at month 3 for a maximum 21-months duration. Dasatinib was continued thereafter. The primary endpoint was the cumulative rate of molecular response 4.5 log (MR
Substances chimiques
Dasatinib
RBZ1571X5H
peginterferon alfa-2b
G8RGG88B68
diazobenzenesulfonic acid
Z0105S98AO
Interferon-alpha
0
Polyethylene Glycols
3WJQ0SDW1A
Banques de données
ClinicalTrials.gov
['NCT01872442']
Types de publication
Multicenter Study
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
175-186Subventions
Organisme : Bristol-Myers Squibb
Organisme : Merck
Informations de copyright
© 2022 British Society for Haematology and John Wiley & Sons Ltd.
Références
Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260-70.
Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C, et al. Final 5-year study results of DASISION: the Dasatinib versus imatinib study in treatment-Naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34(20):2333-40.
Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-84.
Dulucq S, Astrugue C, Etienne G, Mahon F, Benard A. Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta-analysis of studies over the last ten years. Br J Haematol. 2020;189(3):452-68.
Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, 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(6):747-57.
Mahon FX, Delbrel X, Cony-Makhoul P, Fabères C, Boiron JM, Barthe C, et al. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(1):214-20.
Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010;363(26):2511-21.
Johnson-Ansah H, Guilhot J, Rousselot P, Rea D, Legros L, Rigal-Huguet F, et al. Tolerability and efficacy of pegylated interferon-α-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia: interferon for chronic myeloid leukemia. Cancer. 2013;119(24):4284-9.
Nicolini FE, Etienne G, Dubruille V, Roy L, Huguet F, Legros L, et al. Nilotinib and peginterferon alfa-2a for newly diagnosed chronic-phase chronic myeloid leukaemia (NiloPeg): a multicentre, non-randomised, open-label phase 2 study. Lancet Haematol. 2015;2(1):e37-46.
Hadzijusufovic E, Albrecht-Schgoer K, Huber K, Hoermann G, Grebien F, Eisenwort G, et al. Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a primary target site. Leukemia. 2017;31(11):2388-97.
for the Nordic CML Study Group (NCMLSG), Hjorth-Hansen H, Stentoft J, et al. Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients. Leukemia. 2016;30(9):1853-60.
Rousselot P, Mollica L, Guilhot J, Guerci A, Nicolini FE, Etienne G, et al. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. Br J Haematol. 2021;194(2):393-402.
Simonsson B, Gedde-Dahl T, Markevärn B, Remes K, Stentoft J, Almqvist A, et al. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood. 2011;118(12):3228-35.
Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872-84.
Cross NCP, White HE, Müller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 2012;26(10):2172-5.
Wang W, Cortes JE, Tang G, Khoury JD, Wang S, Bueso-Ramos CE, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood. 2016;127(22):2742-50.
Flygt H, Söderlund S, Stentoft J, Richter J, Koskenvesa P, Mustjoki S, et al. Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP: five-year follow-up of the NordCML007 study. Eur J Haematol. 2021;107(6):617-23.
Hehlmann R, Müller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol. 2014;32(5):415-23.
Guilhot F, Rigal-Huguet F, Guilhot J, Guerci-Bresler AP, Maloisel F, Rea D, et al. Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial. Leukemia. 2021;35(8):2332-45.
Baccarani M, Martinelli G, Rosti G, Trabacchi E, Testoni N, Bassi S, et al. Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia. Blood. 2004;104(13):4245-51.
Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119(5):1123-9.
Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231-7.
Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30(5):1044-54.
Nicolini FE, Etienne G, Huguet F, Guerci-Bresler A, Charbonnier A, Escoffre-Barbe M, et al. The combination of nilotinib + pegylated IFN alpha 2a provides somewhat higher cumulative incidence rates of MR4.5 at M36 versus nilotinib alone in newly diagnosed CP CML patients. Updated results of the petals phase III National study. Blood. 2019;134(Supplement_1):494.
Roux C, Nicolini F-E, Rea D, Niault M, Mollica L, Berger F, et al. Reversible lymph node follicular hyperplasia associated with dasatinib treatment of chronic myeloid leukemia in chronic phase. Blood. 2013;122(17):3082-4.
Kantarjian HM, Hughes TP, Larson RA, Kim DW, Issaragrisil S, le Coutre P, et al. Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis. Leukemia. 2021;35(2):440-53.
Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gómez Casares MT, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31(7):1525-31.
Kimura S, Imagawa J, Murai K, Hino M, Kitawaki T, Okada M, et al. Treatment-free remission after first-line dasatinib discontinuation in patients with chronic myeloid leukaemia (first-line DADI trial): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2020;7(3):e218-25.
Radich JP, Hochhaus A, Masszi T, Hellmann A, Stentoft J, Casares MTG, et al. Treatment-free remission following frontline nilotinib in patients with chronic phase chronic myeloid leukemia: 5-year update of the ENESTfreedom trial. Leukemia. 2021;35(5):1344-55.