Newer Generation TKIs May Be More Effective Than Imatinib for CP-CML

The newer group of tyrosine kinase inhibitors (TKIs), such as dasatinib, nilotinib, and bosutinib, showed greater effectiveness as a category, in terms of major molecular response and prevention of accelerated phase/blast crisis progression, than imatinib for the first-line treatment of patients with newly diagnosed chronic myeloid leukemia in chronic phase (CP-CML), a study published in the journal Clinical Lymphoma, Myeloma & Leukemia has shown.¹

Because there are some data that suggested that the degree of benefit from first-line newer TKIs approved by the U.S. Food and Drug Administration (FDA) over imatinib in high-risk patients is greater than those with intermediate or low risk, researchers sought to compare the efficacy of newer TKIs as a category with imatinib.

Further, researchers evaluated the prognostic impact of risk stratification on cytogenetic and major molecular response.

For the study, researchers systematically reviewed data from randomized controlled trials that compared the efficacy of first-line treatment with newer generation TKIs with that of imatinib in adult patients with CP-CML.

Results showed that there were no statistically significant differences between imatinib and newer generation TKIs in terms of complete cytogenetic response, progression-free survival, or overall survival.

However, researchers found that patients treated with newer generation TKI demonstrated a significantly higher likelihood of having a major molecular response (RR, 0.76; 95% CI: 0.63 – 0.91; P = .003) and a reduced risk for progressing to accelerated phase or blast crisis (RR, 0.37; 95% CI, 0.20 – 0.67; P = .001) compared with imatinib-treated patients.

When researchers compared newer generation TKIs with each other, they found that nilotinib, dasatinib, and radotinib showed significantly higher rates of complete cytogenetic response than bosutinib or ponatinib.

The study also demonstrated that risk stratification using the Sokal or Hasford risk score had no impact on the likelihood of achieving a complete cytogenetic response or major molecular response.

Reference

1. Yun S, Vincelette ND, Segar JM, et al. Comparative effectiveness of newer tyrosine kinase inhibitors versus imatinib in the first-line treatment of chronic phase chronic myeloid leukemia across risk groups: a systematic review and meta-analysis of eight randomized trials [published online ahead of print March 29, 2016]. Clin Lymphoma Myeloma Leuk. doi: 10.1016/j.clml.2016.03.003.