Analysis Identifies Ponatinib as Optimal Third-Line TKI for CML in Chronic Phase

The tyrosine kinase inhibitor (TKI) ponatinib may be the optimal third-line therapy for patients with chronic myeloid leukemia (CML) in the chronic phase, according to a study presented at the 2022 ASH Annual Meeting.

Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, and colleagues retrospectively combined data from 354 patients with CML in chronic phase who had received third-line TKI therapy to try to determine the optimal treatment approach. Patients had been treated at MD Anderson (58%), in the PACE study (18%), or in the OPTIC (25%) study.

Third-line TKIs received included dasatinib (19%), nilotinib (18%), bosutinib (11%), and ponatinib (51%). At the time of third-line therapy, the median BCR::ABL1 level was 16.3% on the international scale.

Dr. Jabbour and colleagues conducted a propensity score matching analysis using age at the time of third-line therapy, gender, race, comorbidity, prior TKI therapy, duration of prior TKI therapy, best prior response during front-line and second-line TKI therapy, and several other factors. They identified 96 patients for both the second-generation TKI and ponatinib groups. Median follow-up after propensity score matching was 46 months.

There was a tendency of deeper response with ponatinib at baseline BCR::ABL1 levels of >1-10% and >0.1-1% before and after propensity score matching. Both older age at the time of third-line therapy and higher BCR::ABL1 levels were adverse prognostic factors for survival.

The use of ponatinib in the third-line was associated with a favorable survival (hazard ratio, 0.435; 95% CI, 0.253-0.748; P=.003). After matching, the four-year progression-free survival was 58% for second-generation TKIs and 75% for ponatinib (P=.0099) and the four-year overall survival rates were 78% and 87%, respectively.

Based on these results, Dr. Jabbour and colleagues concluded that “third-line ponatinib therapy is optimal selection for patients with CML-CP who failed prior two TKI therapies in the absence of T315I mutation.”

Reference

Jabbour E, Sasaki K, Issa GC, et al. Outcome of Third-Line Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia in Chronic Phase: A Propensity Score Analysis. Abstract #333. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.