Advertisement

The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors

Elias Jabbour, Hagop Kantarjian, Susan O'Brien, Jenny Shan, Alfonso Quintas-Cardama, Stefan Faderl, Guillermo Garcia-Manero, Farhad Ravandi, Mary Beth Rios and Jorge Cortes

Abstract

We analyzed the association between achievement of early complete cytogenetic response (CCyR) and event-free (EFS) and overall survival (OS) in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib 400 mg (n=73), or imatinib 800 mg daily (n=208), or second generation tyrosine kinase inhibitors (2ndTKI; n=154). The overall CCyR rates were 87 %, 91%, and 96%, respectively (p = 0.06) and major molecular response (MMR) rates 77%, 87%, and 89%, respectively (p = 0.05). Their 3-year EFS rates were 85%, 92%, and 97% (p=0.01), and OS rates 93%, 97%, and 100% (p = 0.18), respectively. By landmark analysis, patients with 3-, 6-, and 12-month CCyR had significantly better outcome: 3-year EFS rates of 98%, 97%, and 98%, and OS rates of 99%, 99%, and 99%, respectively compared to 83%, 72%, and 67% and 95%, 90%, and 94%, in patients who did not achieve a CCyR. Among patients achieving CCyR at 12months, the depth of molecular response was not associated with differences in OS or EFS. In conclusion, 2ndTKI induced higher rates of CCyR and MMR than imatinib. The achievement of early CCyR remains a major determinant of CML outcome regardless of whether MMR is achieved or not.

  • Submitted April 12, 2011.
  • Accepted July 12, 2011.