Evaluating ponatinib treatment in any phase of treatment in patients with chronic myeloid leukemia resistant or intolerant to other tyrosine kinase inhibitors

This study aimed to investigate the safety and effectiveness of ponatinib (Iclusig) in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs). 

This study concluded that ponatinib was effective in heavily pretreated patients when administered in any phase of CML. 

Tyrosine kinase inhibitors (TKIs) are a type of targeted therapy. They have greatly improved treatment outcomes for most patients with chronic myeloid leukemia (CML). Ponatinib is a newer type (third generation) of TKI that can be used for patients with resistant CML.

Clinical trials have shown ponatinib to be effective in patients with resistant or intolerant CML. However, the effectiveness and safety of ponatinib in patients with TKI-resistant or intolerant CML in the real world and according to the CML phase are still unknown. 

This study involved 43 patients with CML. 23 patients started treatment with ponatinib in the chronic phase (CP), 3 started in accelerated phase (AP), and 17 where in the blast phase (BP). Patietns were followed up for an average of 35.4 months. 

The average time on ponatinib treatment for the CP group was 19.5 months and 31.7 months for the AP group. All patients in the AP group were in CP after 1 month of treatment and remained in CP at the end of the study. After 35.4 months, the progression-free survival (PFS) rate for patients in the CP group was 100%. The estimated 2-year survival rate for the CP and AP patients was 84%. 

In the BP group, the average time on ponatinib was 4.6 months. 59% (10 patients) of these patients were in the CP at 1 month. 1 patient was in AP after 1 month and achieved CP at the end of the study. The other 6 patients (35%) were still in BP after 1 month and at the end of the study. 

For all patients, the average survival was not reached (exceeded the follow-up period) and the estimated 2-year survival was 60%.

44% of patients experienced side effects. Significant cardiovascular (heart and blood vessel) side effects occurred in 28% of patients. There was no difference in side effects in patients that started treatment in the CP, AP, or BP phases. 

This study concluded that ponatinib was effective in a significant proportion of patients with heavily pre-treated CML that was intolerant or nonresponsive to other TKIs and durable responses were achieved in both CP and AP/BP groups. 

This study had a small sample size. Further, larger studies are needed.