T315I is the most common mutation in TKI-resistant CML1-3

Among patients with a BCR::ABL1 mutation, the frequency of the T315I mutation was 10-27%.2,4-6,a

Reviews of the clinical literature showed that:

  • Development of the T315I mutation leads to resistance with first- or second-generation TKIs1,7
  • BCR::ABL1 mutation testing helps inform TKI treatment choice7,8

Prior to the approval of therapies in T315I+ CML, the overall survival of T315I+ CML patients at 5 years was 0-30%1,9,b

aThe frequency of the T315I mutation was 10% in the Qin et al (n=7/74), 27% in the Lewandowski et al (n=3/11), and 12% in the Soverini et al (n=15/127) publications.4-6

bData from two studies. Nicolini, 2013 (n=64) measured 5-year OS from the time of imatinib resistance and Nicolini, 2009 (n=82) measured 5-year OS from the time of T315I mutation detection.1,9

ICLUSIG is the only third-generation pan-mutational TKI that delivers proven long-term efficacy for patients with a T315I mutation10-12

Category 2A, preferred NCCN recommendation.

Ponatinib is the preferred treatment option for patients with a T315I mutation.  It is also a treatment option for CP-CML with resistance or intolerance to at least two prior TKIs, or for patients with AP-CML or BP-CML for whom no other TKI is indicated.7

OS 66 percent estimated at 5 years. PFS 50 percent estimated at 5 years.
70 percent of CP-CML patients with a T315I mutation in the PACE trial (n=64) achieved MCyR and responses were deep and durable.

PACE trial design

PACE was a single-arm, open-label, international, multicenter, phase 2 trial in adult CML or Ph+ ALL patients whose disease was considered to be resistant or intolerant to a prior kinase inhibitor or who had T315I mutation (N=449; n=64 T315I-positive CML). At study completion, the mediation duration of follow-up for the trial (all cohorts) was 40.5 months (range 0.1 months to 79.5 months). The major efficacy outcome measure (primary endpoint) for patients with CP-CML was MCyR by 12 months, which included CCyR and PCyR.11,12

ICLUSIG 5-year safety data in CP-CML

ICLUSIG simple once-daily oral dosing

CCyR=complete cytogenetic response; CML=chronic myeloid leukemia; CP‑CML=chronic phase chronic myeloid leukemia; MCyR=major cytogenetic response; OS=overall survival; PCyR= partial cytogenetic response; Ph+ ALL= Philadelphia Chromosome positive acute lymphoblastic leukemia; TKI=tyrosine kinase inhibitor.