The clinical significance of achieving different levels of cytogenetic response in patients with chronic phase chronic myeloid leukemia after failure to front-line therapy: Is complete cytogenetic response the only desirable endpoint?

Jorge Cortes, Alfonso Quintas-Cardama, Elias Jabbour, Susan O'Brien, Srdan Verstovsek, Gautam Borthakur, Farhad Ravandi, Guillermo Garcia-Manero, Elizabeth Burton, Jenny Shan, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

Many patients with chronic myeloid leukemia who have failed initial therapy with a tyrosine kinase inhibitor achieve a cytogenetic response that is not complete (ie, partial or minor). This study analyzes the clinical benefit of such responses and identifies value in achieving such responses. Patients with less than complete cytogenetic response to second-line therapy or beyond should be considered to have benefit from therapy and the value of this considered in the context of which alternative options are available. Background: Complete cytogenetic response (CCyR) is the gold standard for response to therapy for patients with chronic myeloid leukemia (CML) because it is associated with a survival benefit. However, patients who have failed initial therapy with a tyrosine kinase inhibitor (TKI) frequently achieve only partial or minor cytogenetic responses. The clinical benefit of such responses is unclear. Patients and Methods: We analyzed the records of all 165 consecutive patients treated in clinical trials with TKI as second-line therapy or beyond after failure to prior imatinib therapy. Results: A CCyR was achieved with second-line TKI therapy or beyond in 52% of patients, whereas 7% achieved a partial cytogenetic response (PCyR), 14% a minor cytogenetic response (mCyR), 14% complete hematologic response (CHR) only, and 17% no response. The 3-year survival probability was 98% for those with CCyR, compared to 83% with PCyR, 83% for mCyR, 76% for CHR, and 71% for no response. Survival free from transformation rates at 3 years were 93%, 73%, 84%, 88%, and 0%, respectively. Conclusions: CCyR is associated with the greatest survival benefit among patients treated with second-line therapy or beyond and remains the optimal cytogenetic goal of therapy. However, patients with partial and minor cytogenetic response derive a benefit compared to patients who have no response. This benefit should be recognized and evaluated against any alternative option available to a given patient before a change in therapy is recommended.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalClinical Lymphoma, Myeloma and Leukemia
Volume11
Issue number5
DOIs
StatePublished - Oct 2011
Externally publishedYes

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

Keywords

  • Chronic myeloid leukemia
  • Complete cytogenetic response
  • Interferon alfa
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

The clinical significance of achieving different levels of cytogenetic response in patients with chronic phase chronic myeloid leukemia after failure to front-line therapy : Is complete cytogenetic response the only desirable endpoint? / Cortes, Jorge; Quintas-Cardama, Alfonso; Jabbour, Elias; O'Brien, Susan; Verstovsek, Srdan; Borthakur, Gautam; Ravandi, Farhad; Garcia-Manero, Guillermo; Burton, Elizabeth; Shan, Jenny; Kantarjian, Hagop.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 11, No. 5, 10.2011, p. 421-426.

Research output: Contribution to journalArticle

Cortes, Jorge ; Quintas-Cardama, Alfonso ; Jabbour, Elias ; O'Brien, Susan ; Verstovsek, Srdan ; Borthakur, Gautam ; Ravandi, Farhad ; Garcia-Manero, Guillermo ; Burton, Elizabeth ; Shan, Jenny ; Kantarjian, Hagop. / The clinical significance of achieving different levels of cytogenetic response in patients with chronic phase chronic myeloid leukemia after failure to front-line therapy : Is complete cytogenetic response the only desirable endpoint?. In: Clinical Lymphoma, Myeloma and Leukemia. 2011 ; Vol. 11, No. 5. pp. 421-426.
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abstract = "Many patients with chronic myeloid leukemia who have failed initial therapy with a tyrosine kinase inhibitor achieve a cytogenetic response that is not complete (ie, partial or minor). This study analyzes the clinical benefit of such responses and identifies value in achieving such responses. Patients with less than complete cytogenetic response to second-line therapy or beyond should be considered to have benefit from therapy and the value of this considered in the context of which alternative options are available. Background: Complete cytogenetic response (CCyR) is the gold standard for response to therapy for patients with chronic myeloid leukemia (CML) because it is associated with a survival benefit. However, patients who have failed initial therapy with a tyrosine kinase inhibitor (TKI) frequently achieve only partial or minor cytogenetic responses. The clinical benefit of such responses is unclear. Patients and Methods: We analyzed the records of all 165 consecutive patients treated in clinical trials with TKI as second-line therapy or beyond after failure to prior imatinib therapy. Results: A CCyR was achieved with second-line TKI therapy or beyond in 52{\%} of patients, whereas 7{\%} achieved a partial cytogenetic response (PCyR), 14{\%} a minor cytogenetic response (mCyR), 14{\%} complete hematologic response (CHR) only, and 17{\%} no response. The 3-year survival probability was 98{\%} for those with CCyR, compared to 83{\%} with PCyR, 83{\%} for mCyR, 76{\%} for CHR, and 71{\%} for no response. Survival free from transformation rates at 3 years were 93{\%}, 73{\%}, 84{\%}, 88{\%}, and 0{\%}, respectively. Conclusions: CCyR is associated with the greatest survival benefit among patients treated with second-line therapy or beyond and remains the optimal cytogenetic goal of therapy. However, patients with partial and minor cytogenetic response derive a benefit compared to patients who have no response. This benefit should be recognized and evaluated against any alternative option available to a given patient before a change in therapy is recommended.",
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