Cycling second-generation TKIs in resistant patients is associated with reduced response rates and poor survival1-5
aData from the Ibrahim et al (n=7), García‑Gutiérrez et al (n=17), and Garg et al (n=12) publications. Ibrahim et al defined hematologic resistance as either failure to achieve a CHR or loss of a previously achieved CHR. Garg et al included patients with CP‑CML who developed resistance to second‑line TKI treatment without acquiring new BCR::ABL1 mutations. The percentage listed above includes only those patients with CP‑CML who developed resistance to second‑line treatment and had acquired novel BCR::ABL1 mutations after developing resistance. Garg et al defined resistance as failure to achieve a CHR (CP only) or any hematologic response (AP or BP) after 3 months of therapy, persistence of 100% Philadelphia chromosome (Ph)‑positive metaphases after 6 months of therapy, or 35% or more after 12 months of therapy, transformation to AP or BP, or loss of cytogenetic response or CHR at any time during the course of therapy.3-5
Resistance to TKIs occurs by two mechanisms6,7:
- Primary: Lack of response to initial TKI therapy
- Secondary: Loss of response, potentially due to BCR::ABL1 mutations and disease progression
Recognize the critical moment and assess your treatment path forward
AP=accelerated phase; BP=blast phase; CCyR=complete cytogenetic response; CHR=complete hematologic response; CP=chronic phase; CP-CML=chronic phase chronic myeloid leukemia; CML=chronic myeloid leukemia; TKI=tyrosine kinase inhibitor.