TKI resistance is a critical moment in the treatment of CP-CML1

Treatment-resistant patients need a therapy with depth and durability of response in the third line

Cycling second-generation TKIs in resistant patients is associated with reduced response rates and poor survival1-5

Greater than or equal to 82 percent of patients with CP-CML resistant to second-generation TKI do not achieve CCyR with dasatinib, nilotinib, bosutinib in the third line.

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

Reconsider sequential use of second-generation TKIs in the third line when patients with CP-CML demonstrate resistance to 2 prior TKIs.

For patients heavily pretreated with TKIs, consider ICLUSIG

For patients with CML, regardless of mutations, consider ICLUSIG

ICLUSIG is a third-generation pan-mutational TKI

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.