Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors

Lorenzo Falchi, Hagop M. Kantarjian, Xuemei Wang, Dushyant Verma, Alfonso Quintás-Cardama, Susan O'Brien, Elias J. Jabbour, Farhad Ravandi-Kashani, Gautam Borthakur, Guillermo Garcia-Manero, Srdan Verstovsek, Jan A. Burger, Raja Luthra, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

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 (susMR4·5) 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 susMR4·5 does not appear to further reduce the risk of transformation or death.

Original languageEnglish (US)
Pages (from-to)1024-1029
Number of pages6
JournalAmerican Journal of Hematology
Volume88
Issue number12
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Survival
Leukemia, Myeloid, Chronic Phase
Cytogenetics

ASJC Scopus subject areas

  • Hematology

Cite this

Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. / Falchi, Lorenzo; Kantarjian, Hagop M.; Wang, Xuemei; Verma, Dushyant; Quintás-Cardama, Alfonso; O'Brien, Susan; Jabbour, Elias J.; Ravandi-Kashani, Farhad; Borthakur, Gautam; Garcia-Manero, Guillermo; Verstovsek, Srdan; Burger, Jan A.; Luthra, Raja; Cortes, Jorge E.

In: American Journal of Hematology, Vol. 88, No. 12, 01.12.2013, p. 1024-1029.

Research output: Contribution to journalArticle

Falchi, L, Kantarjian, HM, Wang, X, Verma, D, Quintás-Cardama, A, O'Brien, S, Jabbour, EJ, Ravandi-Kashani, F, Borthakur, G, Garcia-Manero, G, Verstovsek, S, Burger, JA, Luthra, R & Cortes, JE 2013, 'Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors', American Journal of Hematology, vol. 88, no. 12, pp. 1024-1029. https://doi.org/10.1002/ajh.23560
Falchi, Lorenzo ; Kantarjian, Hagop M. ; Wang, Xuemei ; Verma, Dushyant ; Quintás-Cardama, Alfonso ; O'Brien, Susan ; Jabbour, Elias J. ; Ravandi-Kashani, Farhad ; Borthakur, Gautam ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Burger, Jan A. ; Luthra, Raja ; Cortes, Jorge E. / Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. In: American Journal of Hematology. 2013 ; Vol. 88, No. 12. pp. 1024-1029.
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abstract = "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 (susMR4·5) 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 susMR4·5 does not appear to further reduce the risk of transformation or death.",
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AU - Verma, Dushyant

AU - Quintás-Cardama, Alfonso

AU - O'Brien, Susan

AU - Jabbour, Elias J.

AU - Ravandi-Kashani, Farhad

AU - Borthakur, Gautam

AU - Garcia-Manero, Guillermo

AU - Verstovsek, Srdan

AU - Burger, Jan A.

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