A NATIONWIDE OBSERVATIONAL STUDY OF THE ISRAELI EXPERIENCE WITH PONATINIB OUTSIDE CLINICAL TRIALS IN CHRONIC MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Abulafia A. 06/09/16; 134738; PB1838
Dr. Adi Abulafia
Contributions
Contributions
Abstract
Abstract: PB1838
Type: Publication Only
Background
Ponatinib is an oral tyrosine kinase inhibitor (TKI) that has been designed to be effective also in patients who harbor the TKI-refractory threonine to isoleucine mutation at position 315 (T315I). In December 2014 the drug was granted an accelerated approval by the FDA, based on the promising results from the phase II PACE trial. Nevertheless, the wide use of the drug has been limited due to safety matters, in particular arterial thrombotic complications, reported in up to 17% of patients. Currently, there is little real-life information regarding the use of ponatinib outside of clinical trials.
Aims
1) To characterize patients with chronic myeloid leukemia (CML) who received ponatinib.2) To determine safety profile of ponatinib outside clinical trials.3) To assess the efficacy of ponatinib outside clinical trials.
Methods
Between 4.2011 and 7.2015 (51 months) 24 patients in 7 medicals with CML received ponatinib. We reviewed the medical records of these patients and asked their physicians to rank the quality of life of their patients on a 1 to 5 scale.
Results
The median age was 44 years (rang: 23 to 79) and most were in accelerated (21%, N=5) or blast crisis (41%, N=10) phases at time ponatinib was initiated. Prior to ponatinib, the patients were treated for a median of 55 months (range: 1 to 215) with 1 to 3 different TKIs (median: 3). Thirteen received at least one course of chemotherapy or interferon-α, and two underwent allogeneic bone marrow transplantation. Mutations at the bcr-abl DNA binding domain were detected in 11 patients (69%) and T315I mutation in 8 of those.Based on the medical history, 48% were at-risk for vascular complications either because of prior cerebrovascular event or myocardial infarction (18%) or because of vascular risk factors (30%). Baseline ECG and cardiac ECHO studies were available in 11 patients and none had significant structural or functional pathology.Patients were followed between1 to 34 months at time of analysis (median: 6 months) and during this time 4 patients died and 14 were still receiving ponatinib. Patients discontinued the treatment either because of major cardiovascular events (N=3), severe pancytopenia (N=1), planned bone-marrow transplantation (N=1) or because they were lost to follow-up (N=1). Seventeen patients were available for response assessment at time of analysis and the overall response rate was 77% (N=13). Five of six patients at chronic phase achieved either complete or major molecular response. Eight patients at accelerated phase or at blast crisis (8/11, 72%) achieved either hematological (5/11, 45%) or molecular response (3/11, 27%). Two of those, with hematological response, underwent allogeneic bone marrow transplantation. The median subjective scoring of ponatinib contribution to the quality of life of patients was 2.4 (range 1 to 5). Physicians that gave low scoring mentioned Severe weakness, myalgia and cytopenias were mentioned as a major concern.
Conclusion
In real- life setting ponatinib is generally used as a last resort. In our cohort, it was almost exclusively given to patients who experienced failure to previous TKIs. Only one third of patients tolerated the recommended dose of 45mg. Yet, response rate was still relatively high, suggesting that a daily dose of 30mg might be appropriate.With only 6 months of follow-up we documented 3 cardiovascular events (12%) that prompted discontinuation of the drug.The high response rate and overall contribution to quality of life in patients, who already experienced failure of other TKIs, support the use of ponatinib in this setting.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
Type: Publication Only
Background
Ponatinib is an oral tyrosine kinase inhibitor (TKI) that has been designed to be effective also in patients who harbor the TKI-refractory threonine to isoleucine mutation at position 315 (T315I). In December 2014 the drug was granted an accelerated approval by the FDA, based on the promising results from the phase II PACE trial. Nevertheless, the wide use of the drug has been limited due to safety matters, in particular arterial thrombotic complications, reported in up to 17% of patients. Currently, there is little real-life information regarding the use of ponatinib outside of clinical trials.
Aims
1) To characterize patients with chronic myeloid leukemia (CML) who received ponatinib.2) To determine safety profile of ponatinib outside clinical trials.3) To assess the efficacy of ponatinib outside clinical trials.
Methods
Between 4.2011 and 7.2015 (51 months) 24 patients in 7 medicals with CML received ponatinib. We reviewed the medical records of these patients and asked their physicians to rank the quality of life of their patients on a 1 to 5 scale.
Results
The median age was 44 years (rang: 23 to 79) and most were in accelerated (21%, N=5) or blast crisis (41%, N=10) phases at time ponatinib was initiated. Prior to ponatinib, the patients were treated for a median of 55 months (range: 1 to 215) with 1 to 3 different TKIs (median: 3). Thirteen received at least one course of chemotherapy or interferon-α, and two underwent allogeneic bone marrow transplantation. Mutations at the bcr-abl DNA binding domain were detected in 11 patients (69%) and T315I mutation in 8 of those.Based on the medical history, 48% were at-risk for vascular complications either because of prior cerebrovascular event or myocardial infarction (18%) or because of vascular risk factors (30%). Baseline ECG and cardiac ECHO studies were available in 11 patients and none had significant structural or functional pathology.Patients were followed between1 to 34 months at time of analysis (median: 6 months) and during this time 4 patients died and 14 were still receiving ponatinib. Patients discontinued the treatment either because of major cardiovascular events (N=3), severe pancytopenia (N=1), planned bone-marrow transplantation (N=1) or because they were lost to follow-up (N=1). Seventeen patients were available for response assessment at time of analysis and the overall response rate was 77% (N=13). Five of six patients at chronic phase achieved either complete or major molecular response. Eight patients at accelerated phase or at blast crisis (8/11, 72%) achieved either hematological (5/11, 45%) or molecular response (3/11, 27%). Two of those, with hematological response, underwent allogeneic bone marrow transplantation. The median subjective scoring of ponatinib contribution to the quality of life of patients was 2.4 (range 1 to 5). Physicians that gave low scoring mentioned Severe weakness, myalgia and cytopenias were mentioned as a major concern.
Conclusion
In real- life setting ponatinib is generally used as a last resort. In our cohort, it was almost exclusively given to patients who experienced failure to previous TKIs. Only one third of patients tolerated the recommended dose of 45mg. Yet, response rate was still relatively high, suggesting that a daily dose of 30mg might be appropriate.With only 6 months of follow-up we documented 3 cardiovascular events (12%) that prompted discontinuation of the drug.The high response rate and overall contribution to quality of life in patients, who already experienced failure of other TKIs, support the use of ponatinib in this setting.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
Abstract: PB1838
Type: Publication Only
Background
Ponatinib is an oral tyrosine kinase inhibitor (TKI) that has been designed to be effective also in patients who harbor the TKI-refractory threonine to isoleucine mutation at position 315 (T315I). In December 2014 the drug was granted an accelerated approval by the FDA, based on the promising results from the phase II PACE trial. Nevertheless, the wide use of the drug has been limited due to safety matters, in particular arterial thrombotic complications, reported in up to 17% of patients. Currently, there is little real-life information regarding the use of ponatinib outside of clinical trials.
Aims
1) To characterize patients with chronic myeloid leukemia (CML) who received ponatinib.2) To determine safety profile of ponatinib outside clinical trials.3) To assess the efficacy of ponatinib outside clinical trials.
Methods
Between 4.2011 and 7.2015 (51 months) 24 patients in 7 medicals with CML received ponatinib. We reviewed the medical records of these patients and asked their physicians to rank the quality of life of their patients on a 1 to 5 scale.
Results
The median age was 44 years (rang: 23 to 79) and most were in accelerated (21%, N=5) or blast crisis (41%, N=10) phases at time ponatinib was initiated. Prior to ponatinib, the patients were treated for a median of 55 months (range: 1 to 215) with 1 to 3 different TKIs (median: 3). Thirteen received at least one course of chemotherapy or interferon-α, and two underwent allogeneic bone marrow transplantation. Mutations at the bcr-abl DNA binding domain were detected in 11 patients (69%) and T315I mutation in 8 of those.Based on the medical history, 48% were at-risk for vascular complications either because of prior cerebrovascular event or myocardial infarction (18%) or because of vascular risk factors (30%). Baseline ECG and cardiac ECHO studies were available in 11 patients and none had significant structural or functional pathology.Patients were followed between1 to 34 months at time of analysis (median: 6 months) and during this time 4 patients died and 14 were still receiving ponatinib. Patients discontinued the treatment either because of major cardiovascular events (N=3), severe pancytopenia (N=1), planned bone-marrow transplantation (N=1) or because they were lost to follow-up (N=1). Seventeen patients were available for response assessment at time of analysis and the overall response rate was 77% (N=13). Five of six patients at chronic phase achieved either complete or major molecular response. Eight patients at accelerated phase or at blast crisis (8/11, 72%) achieved either hematological (5/11, 45%) or molecular response (3/11, 27%). Two of those, with hematological response, underwent allogeneic bone marrow transplantation. The median subjective scoring of ponatinib contribution to the quality of life of patients was 2.4 (range 1 to 5). Physicians that gave low scoring mentioned Severe weakness, myalgia and cytopenias were mentioned as a major concern.
Conclusion
In real- life setting ponatinib is generally used as a last resort. In our cohort, it was almost exclusively given to patients who experienced failure to previous TKIs. Only one third of patients tolerated the recommended dose of 45mg. Yet, response rate was still relatively high, suggesting that a daily dose of 30mg might be appropriate.With only 6 months of follow-up we documented 3 cardiovascular events (12%) that prompted discontinuation of the drug.The high response rate and overall contribution to quality of life in patients, who already experienced failure of other TKIs, support the use of ponatinib in this setting.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
Type: Publication Only
Background
Ponatinib is an oral tyrosine kinase inhibitor (TKI) that has been designed to be effective also in patients who harbor the TKI-refractory threonine to isoleucine mutation at position 315 (T315I). In December 2014 the drug was granted an accelerated approval by the FDA, based on the promising results from the phase II PACE trial. Nevertheless, the wide use of the drug has been limited due to safety matters, in particular arterial thrombotic complications, reported in up to 17% of patients. Currently, there is little real-life information regarding the use of ponatinib outside of clinical trials.
Aims
1) To characterize patients with chronic myeloid leukemia (CML) who received ponatinib.2) To determine safety profile of ponatinib outside clinical trials.3) To assess the efficacy of ponatinib outside clinical trials.
Methods
Between 4.2011 and 7.2015 (51 months) 24 patients in 7 medicals with CML received ponatinib. We reviewed the medical records of these patients and asked their physicians to rank the quality of life of their patients on a 1 to 5 scale.
Results
The median age was 44 years (rang: 23 to 79) and most were in accelerated (21%, N=5) or blast crisis (41%, N=10) phases at time ponatinib was initiated. Prior to ponatinib, the patients were treated for a median of 55 months (range: 1 to 215) with 1 to 3 different TKIs (median: 3). Thirteen received at least one course of chemotherapy or interferon-α, and two underwent allogeneic bone marrow transplantation. Mutations at the bcr-abl DNA binding domain were detected in 11 patients (69%) and T315I mutation in 8 of those.Based on the medical history, 48% were at-risk for vascular complications either because of prior cerebrovascular event or myocardial infarction (18%) or because of vascular risk factors (30%). Baseline ECG and cardiac ECHO studies were available in 11 patients and none had significant structural or functional pathology.Patients were followed between1 to 34 months at time of analysis (median: 6 months) and during this time 4 patients died and 14 were still receiving ponatinib. Patients discontinued the treatment either because of major cardiovascular events (N=3), severe pancytopenia (N=1), planned bone-marrow transplantation (N=1) or because they were lost to follow-up (N=1). Seventeen patients were available for response assessment at time of analysis and the overall response rate was 77% (N=13). Five of six patients at chronic phase achieved either complete or major molecular response. Eight patients at accelerated phase or at blast crisis (8/11, 72%) achieved either hematological (5/11, 45%) or molecular response (3/11, 27%). Two of those, with hematological response, underwent allogeneic bone marrow transplantation. The median subjective scoring of ponatinib contribution to the quality of life of patients was 2.4 (range 1 to 5). Physicians that gave low scoring mentioned Severe weakness, myalgia and cytopenias were mentioned as a major concern.
Conclusion
In real- life setting ponatinib is generally used as a last resort. In our cohort, it was almost exclusively given to patients who experienced failure to previous TKIs. Only one third of patients tolerated the recommended dose of 45mg. Yet, response rate was still relatively high, suggesting that a daily dose of 30mg might be appropriate.With only 6 months of follow-up we documented 3 cardiovascular events (12%) that prompted discontinuation of the drug.The high response rate and overall contribution to quality of life in patients, who already experienced failure of other TKIs, support the use of ponatinib in this setting.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
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