Results of Dasatinib Therapy in Patients with Early Chronic-phase Chronic Myeloid Leukemia

Overview

Journal J Clin Oncol

Specialty Oncology

Date 2009 Dec 17

PMID 20008620

Citations 97

Authors

Jorge E Cortes

Dan Jones

Susan OBrien

Elias Jabbour

Farhad Ravandi

Charles Koller

Gautam Borthakur

Brenda Walker

Weiqiang Zhao

Jianqin Shan

Hagop Kantarjian

Affiliations

Soon will be listed here.

Abstract

Purpose: Dasatinib is effective therapy for chronic myeloid leukemia (CML) after imatinib failure. In this study, we investigate the efficacy of dasatinib as initial therapy for patients with CML in early chronic phase.

Patients And Methods: Patients with newly diagnosed CML in early chronic phase were randomly assigned to receive dasatinib 100 mg once daily or 50 mg twice daily as initial therapy.

Results: Among 50 patients observed for at least 3 months, 49 patients (98%) achieved a complete cytogenetic response (CCyR), and 41 patients (82%) achieved a major molecular response (MMR). Responses occurred rapidly, with 94% of patients achieving CCyR by 6 months. There was no difference in response rate by treatment arm. The projected event-free survival rate at 24 months is 88%, and all patients are alive after a median follow-up time of 24 months. Grade >or= 3 neutropenia and thrombocytopenia occurred in 21% and 10% of patients, respectively. Nonhematologic toxicity was usually grade 1 to 2. There was no significant difference in toxicity between the two arms, and the actual median dose at 12 months was 100 mg (range, 20 to 100 mg).

Conclusion: Dasatinib is an effective agent for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR.

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References

Hochhaus A, Baccarani M, Deininger M, Apperley J, Lipton J, Goldberg S . Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008; 22(6):1200-6. DOI: 10.1038/leu.2008.84. View

Roy L, Guilhot J, Krahnke T, Guerci-Bresler A, Druker B, Larson R . Survival advantage from imatinib compared with the combination interferon-alpha plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials. Blood. 2006; 108(5):1478-84. DOI: 10.1182/blood-2006-02-001495. View

de Lavallade H, Apperley J, Khorashad J, Milojkovic D, Reid A, Bua M . Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008; 26(20):3358-63. DOI: 10.1200/JCO.2007.15.8154. View

Bradeen H, Eide C, OHare T, Johnson K, Willis S, Lee F . Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood. 2006; 108(7):2332-8. PMC: 1895563. DOI: 10.1182/blood-2006-02-004580. View

Cortes J, Talpaz M, OBrien S, Jones D, Luthra R, Shan J . Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005; 11(9):3425-32. DOI: 10.1158/1078-0432.CCR-04-2139. View

Cortes J, Kantarjian H . Beyond dose escalation: clinical options for relapse or resistance in chronic myelogenous leukemia. J Natl Compr Canc Netw. 2008; 6 Suppl 2:S22-S30. View

Cortes J, Kantarjian H, Brummendorf T, Kim D, Turkina A, Shen Z . Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011; 118(17):4567-76. PMC: 4916618. DOI: 10.1182/blood-2011-05-355594. View

Lombardo L, Lee F, Chen P, Norris D, Barrish J, Behnia K . Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004; 47(27):6658-61. DOI: 10.1021/jm049486a. View

Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F . Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006; 108(6):1809-20. DOI: 10.1182/blood-2006-02-005686. View

10.

Quintas-Cardama A, Kantarjian H, Jones D, Shan J, Borthakur G, Thomas D . Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy. Blood. 2009; 113(25):6315-21. PMC: 3953080. DOI: 10.1182/blood-2008-07-166694. View

11.

Druker B, Guilhot F, OBrien S, Gathmann I, Kantarjian H, Gattermann N . Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355(23):2408-17. DOI: 10.1056/NEJMoa062867. View

12.

Shah N, Tran C, Lee F, Chen P, Norris D, Sawyers C . Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305(5682):399-401. DOI: 10.1126/science.1099480. View

13.

Kantarjian H, Talpaz M, OBrien S, Garcia-Manero G, Verstovsek S, Giles F . High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004; 103(8):2873-8. DOI: 10.1182/blood-2003-11-3800. View

14.

Kantarjian H, Talpaz M, OBrien S, Jones D, Giles F, Garcia-Manero G . Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood. 2006; 108(6):1835-40. DOI: 10.1182/blood-2006-02-004325. View

15.

Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C . Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002; 346(9):645-52. DOI: 10.1056/NEJMoa011573. View

16.

Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M . Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol. 2008; 27(3):469-71. DOI: 10.1200/JCO.2008.19.8853. View

17.

Shah N, Kantarjian H, Kim D, Rea D, Dorlhiac-Llacer P, Milone J . Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008; 26(19):3204-12. DOI: 10.1200/JCO.2007.14.9260. View

18.

Cortes J, Baccarani M, Guilhot F, Druker B, Branford S, Kim D . Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor.... J Clin Oncol. 2009; 28(3):424-30. PMC: 4979244. DOI: 10.1200/JCO.2009.25.3724. View

19.

Cortes J, Kantarjian H, Goldberg S, Powell B, Giles F, Wetzler M . High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses. J Clin Oncol. 2009; 27(28):4754-9. PMC: 4979200. DOI: 10.1200/JCO.2008.20.3869. View

20.

OBrien S, Guilhot F, Larson R, Gathmann I, Baccarani M, Cervantes F . Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003; 348(11):994-1004. DOI: 10.1056/NEJMoa022457. View