Contributions
Abstract: PB1827
Type: Publication Only
Background
In December 2014 the oral tyrosine kinase inhibitor (TKI), ponatinib was granted an accelerated approval by the FDA based on promising results from the phase II PACE (Ponatinib Ph-ALL and CML evaluation) trial. Yet, nowadays the use of this drug is limited because of safety issues, most notably increased risk of vascular complications. Currently, there is very little real-life information regarding the use of ponatinib outside clinical trials.
Aims
The purpose of the current study is to characterize patients who received ponatinib and to assess the safety profile and efficacy of ponatinib outside clinical trials.
Methods
Data from electronic charts of chronic myeloid leukemia (CML) patients treated with ponatinib were analyzed.
Results
Patients characteristics: Between 4.2011 and 1.2017 (69 months) 37 patients with an initial diagnosis of CML in 9 medical centers in Israel received ponatinib. The median age at time of treatment was 43 years (range: 9 to 82) and approximately half of the patients had chronic phase CML (N= 19, 53%). Based on their medical history, 36% (N=12) were at increased risk for vascular complications. Pre-ponatinib treatments: Patients received at least one other TKI and most received at-least two different TKI-based regimens (N = 28, 76%). Nine patients (25%) underwent hematopoietic stem cell transplantation (HSCT) prior to ponatinib. The time that lapsed from diagnosis until ponatinib initiation ranged considerably (from 1 to 215 months, median 47 months). Indications for ponatinib switch: 26% of patients (N = 9) switched to ponatinib because T315I mutation was detected. The remaining switched either because of progressive disease, i.e. accelerated (N = 5, 14%) or blastic (17%, N = 6, 17%) phases, and 14 (39%) because they experienced loss of previous molecular or cytogenetics response. Only 5% (N = 2) switched because of unacceptable side effects to previous treatments. Treatment with Ponatinib: Patients received ponatinib for a median time of 14 months (range: 1 to 51). The drug started at the recommended dose of 45 mg/day only in 60% (N = 22) of patients and in 24% of them (N=9) the dose was reduced during treatment. The median survival time of patients with ponatinib was 38 months (95%CI: 30 to 47 months) (Figure 1). Patients died because of cerebrovascular event (N = 1), sepsis (N = 2) or graft vs. host disease that developed shortly after HSCT. Response assessment: Response assessment was available for 32 patients (86%). Seventy percent (N = 22) achieved molecular response, of which 60% (N = 13) achieved at least major molecular response. The median time to maximal response was 7 months (range: 3 to 28 months). Drug discontinuation: Twenty four percent (N=9) discontinued ponatinib after a median of 7 months (range: 1 to 18 months) because of disease progression (N = 6) or severe adverse effects in two patients (cerebrovascular event and severe pancytopenia).
Conclusion
In our cohort ponatinib was almost always used in patients who experienced treatment failure to previous TKIs. Still, molecular response was achieved in most patients, even in those with progressive disease in accelerated or blastic phases. The vast majority of patients received reduced doses of ponatinib and although more than one third of patients were at-risk for vascular events, only two patients developed serious life-threatening vascular episodes. In heavily pre-treated patients, ponatinib is effective and safe and can be considered even in patients with cardiovascular risk factors.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Tyrosine kinase inhibitor, Chronic myeloid leukemia
Abstract: PB1827
Type: Publication Only
Background
In December 2014 the oral tyrosine kinase inhibitor (TKI), ponatinib was granted an accelerated approval by the FDA based on promising results from the phase II PACE (Ponatinib Ph-ALL and CML evaluation) trial. Yet, nowadays the use of this drug is limited because of safety issues, most notably increased risk of vascular complications. Currently, there is very little real-life information regarding the use of ponatinib outside clinical trials.
Aims
The purpose of the current study is to characterize patients who received ponatinib and to assess the safety profile and efficacy of ponatinib outside clinical trials.
Methods
Data from electronic charts of chronic myeloid leukemia (CML) patients treated with ponatinib were analyzed.
Results
Patients characteristics: Between 4.2011 and 1.2017 (69 months) 37 patients with an initial diagnosis of CML in 9 medical centers in Israel received ponatinib. The median age at time of treatment was 43 years (range: 9 to 82) and approximately half of the patients had chronic phase CML (N= 19, 53%). Based on their medical history, 36% (N=12) were at increased risk for vascular complications. Pre-ponatinib treatments: Patients received at least one other TKI and most received at-least two different TKI-based regimens (N = 28, 76%). Nine patients (25%) underwent hematopoietic stem cell transplantation (HSCT) prior to ponatinib. The time that lapsed from diagnosis until ponatinib initiation ranged considerably (from 1 to 215 months, median 47 months). Indications for ponatinib switch: 26% of patients (N = 9) switched to ponatinib because T315I mutation was detected. The remaining switched either because of progressive disease, i.e. accelerated (N = 5, 14%) or blastic (17%, N = 6, 17%) phases, and 14 (39%) because they experienced loss of previous molecular or cytogenetics response. Only 5% (N = 2) switched because of unacceptable side effects to previous treatments. Treatment with Ponatinib: Patients received ponatinib for a median time of 14 months (range: 1 to 51). The drug started at the recommended dose of 45 mg/day only in 60% (N = 22) of patients and in 24% of them (N=9) the dose was reduced during treatment. The median survival time of patients with ponatinib was 38 months (95%CI: 30 to 47 months) (Figure 1). Patients died because of cerebrovascular event (N = 1), sepsis (N = 2) or graft vs. host disease that developed shortly after HSCT. Response assessment: Response assessment was available for 32 patients (86%). Seventy percent (N = 22) achieved molecular response, of which 60% (N = 13) achieved at least major molecular response. The median time to maximal response was 7 months (range: 3 to 28 months). Drug discontinuation: Twenty four percent (N=9) discontinued ponatinib after a median of 7 months (range: 1 to 18 months) because of disease progression (N = 6) or severe adverse effects in two patients (cerebrovascular event and severe pancytopenia).
Conclusion
In our cohort ponatinib was almost always used in patients who experienced treatment failure to previous TKIs. Still, molecular response was achieved in most patients, even in those with progressive disease in accelerated or blastic phases. The vast majority of patients received reduced doses of ponatinib and although more than one third of patients were at-risk for vascular events, only two patients developed serious life-threatening vascular episodes. In heavily pre-treated patients, ponatinib is effective and safe and can be considered even in patients with cardiovascular risk factors.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Tyrosine kinase inhibitor, Chronic myeloid leukemia