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Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors
Author(s) -
Falchi Lorenzo,
Kantarjian Hagop M.,
Wang Xuemei,
Verma Dushyant,
QuintásCardama Alfonso,
O'Brien Susan,
Jabbour Elias J.,
RavandiKashani Farhad,
Borthakur Gautam,
GarciaManero Guillermo,
Verstovsek Srdan,
Burger Jan A.,
Luthra Raja,
Cortes Jorge E.
Publication year - 2013
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23560
Subject(s) - nilotinib , dasatinib , medicine , imatinib , myeloid leukemia , imatinib mesylate , oncology , tyrosine kinase inhibitor , tyrosine kinase , cancer , receptor
Most patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKI) achieve complete cytogenetic response (CCyR). An increasing number of patients also achieve deep molecular responses (MR). We determined the frequency and significance of deep MR after TKI therapy for CML in CP. MR included: major molecular response (MMR), MR4, MR4.5, and undetectable transcripts (UND), i.e., BCR‐ABL/ABL of ≤0.1, ≤0.01, ≤0.0032%, and undetectable transcripts, respectively. Four hundred eighty‐three patients received imatinib 400 mg/day (IM400, 71, July 2000 to April 2001), imatinib 800 mg/day (IM800, 204, June 2001 to July 2005), nilotinib (106, July 2005 to date), or dasatinib (102, November 2005 to date). UND rates at 36 months were 18.1, 30.6, 29.2, and 28.6%, respectively. Patients achieving UND have superior transformation‐free survival (TFS) and overall survival (OS) versus those obtaining ≤MMR, but not other MR levels. At the 18‐ and 24‐month landmark analysis, patients achieving UND have no advantage in TFS and OS compared to those achieving a lesser degree of MR. Among patients achieving MR4.5, those who maintain it for ≥2 years ( sus MR4·5) have no additional benefit in TFS or OS. Most patients with early CP CML receiving TKI achieve MMR. BCR‐ABL transcripts become undetectable in a significant fraction of them. Deeper MR at 18 or 24 months are not associated with a benefit in TFS or OS. Furthermore, achieving sus MR4·5 does not appear to further reduce the risk of transformation or death. Am. J. Hematol. 88:1024–1029, 2013. © 2013 Wiley Periodicals, Inc.