TY - JOUR
T1 - The clinical significance of achieving different levels of cytogenetic response in patients with chronic phase chronic myeloid leukemia after failure to front-line therapy
T2 - Is complete cytogenetic response the only desirable endpoint?
AU - Cortes, Jorge
AU - Quintas-Cardama, Alfonso
AU - Jabbour, Elias
AU - O'Brien, Susan
AU - Verstovsek, Srdan
AU - Borthakur, Gautam
AU - Ravandi, Farhad
AU - Garcia-Manero, Guillermo
AU - Burton, Elizabeth
AU - Shan, Jenny
AU - Kantarjian, Hagop
N1 - Funding Information:
Supported in part by grant P01CA049639 from the National Cancer Institute .
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - Chronic myeloid leukemia
KW - Complete cytogenetic response
KW - Interferon alfa
KW - Tyrosine kinase inhibitor
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U2 - 10.1016/j.clml.2011.06.009
DO - 10.1016/j.clml.2011.06.009
M3 - Article
C2 - 21831744
AN - SCOPUS:84856140582
SN - 2152-2650
VL - 11
SP - 421
EP - 426
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 5
ER -