SAFETY AND EFFICACY OF PONATINIB IN REAL WORLD CLINICAL PRACTICE. RESULTS FROM THE SPANISH COMPASSIONATE USE PROGRAM. A GELMC STUDY
(Abstract release date: 05/19/16)
EHA Library. Garcia-Gutierrez V. 06/09/16; 134732; PB1832
Dr. Valentin Garcia-Gutierrez
Contributions
Contributions
Abstract
Abstract: PB1832
Type: Publication Only
Background
In clinical trials, ponatinib has demonstrated excellent efficacy in heavily pretreated chronic myeloid leukemia (CML) patients. However, a high rate of vascular complications has been reported with the standard dose of 45 mg per day, and seems to be associated with previous cardiovascular (CV) risks. Hence, close safety monitoring and tapering of the dose have been recommended, although there are limited data supporting their benefit. Since patients included in clinical trials are a selected population, there is a need of real world data to properly assess the results of ponatinib treatment.
Aims
The purpose of this study is to provide safety and efficacy information from patients treated with ponatinib in real world clinical practice.
Methods
We have retrospectively collected data from 23 patients treated with ponatinib after resistance to previous treatment with tyrosine kinase inhibitors (TKIs). Molecular biology tests were done according to ELN guidelines and BCR-ABL/ABL is expressed as % IS. Clinical and comorbidities information (including CV risk factors were collected before and during ponatinib treatment.
Results
Median age at diagnosis was 56 years (34-83). Most (70%) had CV risk factors and 20% had suffered a previous CV event. The percentage of low, intermediate and high-risk Sokal groups were 25%, 45% and 15%, respectively. Median time of TKIs exposure before ponatinib was 43 months. One patient was treated in accelerated phase (AP), while the rest were in first or second chronic phase (CP). Thirty seven (%) of the patients had previously received 2 TKIs (imatinib, dasatinib, nilotinib, or bosutinib), and N (62%) had received ≥ 3 . At ponatinib start, 69% of patients had not achieved complete cytogenetic response (CCyR) while the rest were in CCyR (including 17% with major molecular response (MMR)). Sixty percent of the patients had one or more BCR-ABL1 kinase domain mutations at the time of ponatinib start (45% had T315I mutation). Median follow-up was 29 months (3-53). Initial daily dose was 45, 30, and 15 mg in 85%, 5%, and 10% of patients, respectively. The initial dose was reduced in half of the patients, either due to side effects or to minimize the CV toxicity. In the last control, ponatinib daily dose was 45 mg, 30 mg and 15 mg in 65%, 10%, and 25% of the patients, respectively. Probabilities to obtain or maintain previous CCyR or MMR were 65% and 25%, respectively. Fifty eight percent of patients without CCyR at baseline achieved CCyR (17% achieving MMR), while 60% of patients with CCyR at baseline improved their molecular response. No differences in the response rates were observed depending on the mutational status or the initial ponatinib dose. By 43 months, event free survival, and progression free survival were 50% and 80%, respectively. At time of analysis, 40% of the patients had discontinued ponatinib due to toxicity (25%), lack of efficacy (25%), hematopoietic stem cell transplantation (37%) or death (13%). Most common non-hematological toxicities were liver toxicity (20%), lipase increase (10%), and hypertension 15%. No CV events were reported during treatment.
Conclusion
Ponatinib was shown to rescue a significant proportion of patients failing prior TKI treatment. It is worth noting that, with of a median follow-up of more than 2 years, no CV events appeared, suggesting that early dose modification could be protective against the occurrence of vascular complications.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Treatment
Type: Publication Only
Background
In clinical trials, ponatinib has demonstrated excellent efficacy in heavily pretreated chronic myeloid leukemia (CML) patients. However, a high rate of vascular complications has been reported with the standard dose of 45 mg per day, and seems to be associated with previous cardiovascular (CV) risks. Hence, close safety monitoring and tapering of the dose have been recommended, although there are limited data supporting their benefit. Since patients included in clinical trials are a selected population, there is a need of real world data to properly assess the results of ponatinib treatment.
Aims
The purpose of this study is to provide safety and efficacy information from patients treated with ponatinib in real world clinical practice.
Methods
We have retrospectively collected data from 23 patients treated with ponatinib after resistance to previous treatment with tyrosine kinase inhibitors (TKIs). Molecular biology tests were done according to ELN guidelines and BCR-ABL/ABL is expressed as % IS. Clinical and comorbidities information (including CV risk factors were collected before and during ponatinib treatment.
Results
Median age at diagnosis was 56 years (34-83). Most (70%) had CV risk factors and 20% had suffered a previous CV event. The percentage of low, intermediate and high-risk Sokal groups were 25%, 45% and 15%, respectively. Median time of TKIs exposure before ponatinib was 43 months. One patient was treated in accelerated phase (AP), while the rest were in first or second chronic phase (CP). Thirty seven (%) of the patients had previously received 2 TKIs (imatinib, dasatinib, nilotinib, or bosutinib), and N (62%) had received ≥ 3 . At ponatinib start, 69% of patients had not achieved complete cytogenetic response (CCyR) while the rest were in CCyR (including 17% with major molecular response (MMR)). Sixty percent of the patients had one or more BCR-ABL1 kinase domain mutations at the time of ponatinib start (45% had T315I mutation). Median follow-up was 29 months (3-53). Initial daily dose was 45, 30, and 15 mg in 85%, 5%, and 10% of patients, respectively. The initial dose was reduced in half of the patients, either due to side effects or to minimize the CV toxicity. In the last control, ponatinib daily dose was 45 mg, 30 mg and 15 mg in 65%, 10%, and 25% of the patients, respectively. Probabilities to obtain or maintain previous CCyR or MMR were 65% and 25%, respectively. Fifty eight percent of patients without CCyR at baseline achieved CCyR (17% achieving MMR), while 60% of patients with CCyR at baseline improved their molecular response. No differences in the response rates were observed depending on the mutational status or the initial ponatinib dose. By 43 months, event free survival, and progression free survival were 50% and 80%, respectively. At time of analysis, 40% of the patients had discontinued ponatinib due to toxicity (25%), lack of efficacy (25%), hematopoietic stem cell transplantation (37%) or death (13%). Most common non-hematological toxicities were liver toxicity (20%), lipase increase (10%), and hypertension 15%. No CV events were reported during treatment.
Conclusion
Ponatinib was shown to rescue a significant proportion of patients failing prior TKI treatment. It is worth noting that, with of a median follow-up of more than 2 years, no CV events appeared, suggesting that early dose modification could be protective against the occurrence of vascular complications.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Treatment
Abstract: PB1832
Type: Publication Only
Background
In clinical trials, ponatinib has demonstrated excellent efficacy in heavily pretreated chronic myeloid leukemia (CML) patients. However, a high rate of vascular complications has been reported with the standard dose of 45 mg per day, and seems to be associated with previous cardiovascular (CV) risks. Hence, close safety monitoring and tapering of the dose have been recommended, although there are limited data supporting their benefit. Since patients included in clinical trials are a selected population, there is a need of real world data to properly assess the results of ponatinib treatment.
Aims
The purpose of this study is to provide safety and efficacy information from patients treated with ponatinib in real world clinical practice.
Methods
We have retrospectively collected data from 23 patients treated with ponatinib after resistance to previous treatment with tyrosine kinase inhibitors (TKIs). Molecular biology tests were done according to ELN guidelines and BCR-ABL/ABL is expressed as % IS. Clinical and comorbidities information (including CV risk factors were collected before and during ponatinib treatment.
Results
Median age at diagnosis was 56 years (34-83). Most (70%) had CV risk factors and 20% had suffered a previous CV event. The percentage of low, intermediate and high-risk Sokal groups were 25%, 45% and 15%, respectively. Median time of TKIs exposure before ponatinib was 43 months. One patient was treated in accelerated phase (AP), while the rest were in first or second chronic phase (CP). Thirty seven (%) of the patients had previously received 2 TKIs (imatinib, dasatinib, nilotinib, or bosutinib), and N (62%) had received ≥ 3 . At ponatinib start, 69% of patients had not achieved complete cytogenetic response (CCyR) while the rest were in CCyR (including 17% with major molecular response (MMR)). Sixty percent of the patients had one or more BCR-ABL1 kinase domain mutations at the time of ponatinib start (45% had T315I mutation). Median follow-up was 29 months (3-53). Initial daily dose was 45, 30, and 15 mg in 85%, 5%, and 10% of patients, respectively. The initial dose was reduced in half of the patients, either due to side effects or to minimize the CV toxicity. In the last control, ponatinib daily dose was 45 mg, 30 mg and 15 mg in 65%, 10%, and 25% of the patients, respectively. Probabilities to obtain or maintain previous CCyR or MMR were 65% and 25%, respectively. Fifty eight percent of patients without CCyR at baseline achieved CCyR (17% achieving MMR), while 60% of patients with CCyR at baseline improved their molecular response. No differences in the response rates were observed depending on the mutational status or the initial ponatinib dose. By 43 months, event free survival, and progression free survival were 50% and 80%, respectively. At time of analysis, 40% of the patients had discontinued ponatinib due to toxicity (25%), lack of efficacy (25%), hematopoietic stem cell transplantation (37%) or death (13%). Most common non-hematological toxicities were liver toxicity (20%), lipase increase (10%), and hypertension 15%. No CV events were reported during treatment.
Conclusion
Ponatinib was shown to rescue a significant proportion of patients failing prior TKI treatment. It is worth noting that, with of a median follow-up of more than 2 years, no CV events appeared, suggesting that early dose modification could be protective against the occurrence of vascular complications.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Treatment
Type: Publication Only
Background
In clinical trials, ponatinib has demonstrated excellent efficacy in heavily pretreated chronic myeloid leukemia (CML) patients. However, a high rate of vascular complications has been reported with the standard dose of 45 mg per day, and seems to be associated with previous cardiovascular (CV) risks. Hence, close safety monitoring and tapering of the dose have been recommended, although there are limited data supporting their benefit. Since patients included in clinical trials are a selected population, there is a need of real world data to properly assess the results of ponatinib treatment.
Aims
The purpose of this study is to provide safety and efficacy information from patients treated with ponatinib in real world clinical practice.
Methods
We have retrospectively collected data from 23 patients treated with ponatinib after resistance to previous treatment with tyrosine kinase inhibitors (TKIs). Molecular biology tests were done according to ELN guidelines and BCR-ABL/ABL is expressed as % IS. Clinical and comorbidities information (including CV risk factors were collected before and during ponatinib treatment.
Results
Median age at diagnosis was 56 years (34-83). Most (70%) had CV risk factors and 20% had suffered a previous CV event. The percentage of low, intermediate and high-risk Sokal groups were 25%, 45% and 15%, respectively. Median time of TKIs exposure before ponatinib was 43 months. One patient was treated in accelerated phase (AP), while the rest were in first or second chronic phase (CP). Thirty seven (%) of the patients had previously received 2 TKIs (imatinib, dasatinib, nilotinib, or bosutinib), and N (62%) had received ≥ 3 . At ponatinib start, 69% of patients had not achieved complete cytogenetic response (CCyR) while the rest were in CCyR (including 17% with major molecular response (MMR)). Sixty percent of the patients had one or more BCR-ABL1 kinase domain mutations at the time of ponatinib start (45% had T315I mutation). Median follow-up was 29 months (3-53). Initial daily dose was 45, 30, and 15 mg in 85%, 5%, and 10% of patients, respectively. The initial dose was reduced in half of the patients, either due to side effects or to minimize the CV toxicity. In the last control, ponatinib daily dose was 45 mg, 30 mg and 15 mg in 65%, 10%, and 25% of the patients, respectively. Probabilities to obtain or maintain previous CCyR or MMR were 65% and 25%, respectively. Fifty eight percent of patients without CCyR at baseline achieved CCyR (17% achieving MMR), while 60% of patients with CCyR at baseline improved their molecular response. No differences in the response rates were observed depending on the mutational status or the initial ponatinib dose. By 43 months, event free survival, and progression free survival were 50% and 80%, respectively. At time of analysis, 40% of the patients had discontinued ponatinib due to toxicity (25%), lack of efficacy (25%), hematopoietic stem cell transplantation (37%) or death (13%). Most common non-hematological toxicities were liver toxicity (20%), lipase increase (10%), and hypertension 15%. No CV events were reported during treatment.
Conclusion
Ponatinib was shown to rescue a significant proportion of patients failing prior TKI treatment. It is worth noting that, with of a median follow-up of more than 2 years, no CV events appeared, suggesting that early dose modification could be protective against the occurrence of vascular complications.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Treatment
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