CLINICAL OUTCOME IN OLDER AML PATIENTS NOT FIT FOR INTENSIVE CHEMOTHERAPY: RESULTS OF THE POPULATION-BASED AMLSG-BIO (NCT01252485) REGISTRY STUDY OF THE GERMAN-AUSTRIAN AML STUDY GROUP
(Abstract release date: 05/21/15)
EHA Library. Schlenk R. 06/13/15; 103168; S512
Disclosure(s): Department of Internal Medicine IIIUUniversity of Ulm
Prof. Richard Schlenk
Contributions
Contributions
Abstract
Abstract: S512
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:00 to 13.06.2015 16:15
Location: Room C2
Background
Comparative population-based outcome data in AML of older patients not fit for intensive chemotherapy are rare. Currently available treatment options outside clinical trials are best supportive care (BSC), decitabine (DAC), azacitidine (AZA), and low-dose cytarabine (LDAC).
Aims
To assess clinical outcome in patients older than 60 years not fit for intensive chemotherapy within the registry/molecular-screening trial AMLSG BiO (NCT01252485).
Methods
Between 2011 and 2014 a total of 2651 patients (median age 72 years, range 60- 94) have been registered. Molecular screening was performed within 48hours for NPM1 and FLT3 mutations as well as for the fusion-genes PML-RARA, RUNX1-RUNX1T1, MYH11-CBFβ. Treatment and outcome data were documented based on medical records and case record forms.
Results
Of the 2651 patients, n=1104 (42%) received intensive chemotherapy, n=88 (3%) AZA, n=162 (6%) DAC, n=250 (9%) LDAC, n=229 (9%) BSC, n=818 (31%) unknown. Of the 729 patients treated non-intensively n=176 (LDAC, n=134; DAC, n=40; AZA, n=1) were treated in clinical trials. Of the remaining 553 patients, the distribution according to treatment was n=116 LDAC, n=122 DAC, n=87 AZA and n=228 BSC. There was no difference in the age distribution between the groups BSC, AZA, DAC, LDAC (p=0.22, median 76 years, range 60-92), cytogenetic risk group according to ELN recommendations (high, 26%; intermediate, 72%; low, 2%; p=0.35), HCT-CI score <3 (p=0.50), but significantly more patients with ECOG performance status >1 (p<0.001) were in the BSC group, however, without difference between the treatment-groups AZA, DAC, LDAC (p=0.76). Patients with a NPM1 mutation were more frequently (p<0.001) found in the BSC (23%) and the LDAC (22%) group compared to AZA (5%) and DAC (10%). Overall, FLT3-ITD and FLT3-TKD were detected rarely and mutually exclusive (3% each) without a difference between the groups (p=0.87, p=0.89). Significantly (p<0.001) higher white blood counts (WBC) at diagnosis were present in the BSC (median, 27/nl) and LDAC (median, 29.6/nl) compared to AZA (median, 3.5/nl) and DAC (median, 5.0/nl), no differences between groups were present for platelets (p=0.97) and hemoglobin (p=0.60). Median, one-year and two-year survival according to the 4 groups (BSC, AZA, DAC, LDAC) are given in the table.
Summary
In older patients with AML treatment with AZA or DAC is in the short-term perspective of one to two years superior to LDAC. However, results beyond 2 years are still dismal for all treatment options.
Keyword(s): AML, Cytarabine, Decitabine
Session topic: AML outcome and clinical trials
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:00 to 13.06.2015 16:15
Location: Room C2
Background
Comparative population-based outcome data in AML of older patients not fit for intensive chemotherapy are rare. Currently available treatment options outside clinical trials are best supportive care (BSC), decitabine (DAC), azacitidine (AZA), and low-dose cytarabine (LDAC).
Aims
To assess clinical outcome in patients older than 60 years not fit for intensive chemotherapy within the registry/molecular-screening trial AMLSG BiO (NCT01252485).
Methods
Between 2011 and 2014 a total of 2651 patients (median age 72 years, range 60- 94) have been registered. Molecular screening was performed within 48hours for NPM1 and FLT3 mutations as well as for the fusion-genes PML-RARA, RUNX1-RUNX1T1, MYH11-CBFβ. Treatment and outcome data were documented based on medical records and case record forms.
Results
Of the 2651 patients, n=1104 (42%) received intensive chemotherapy, n=88 (3%) AZA, n=162 (6%) DAC, n=250 (9%) LDAC, n=229 (9%) BSC, n=818 (31%) unknown. Of the 729 patients treated non-intensively n=176 (LDAC, n=134; DAC, n=40; AZA, n=1) were treated in clinical trials. Of the remaining 553 patients, the distribution according to treatment was n=116 LDAC, n=122 DAC, n=87 AZA and n=228 BSC. There was no difference in the age distribution between the groups BSC, AZA, DAC, LDAC (p=0.22, median 76 years, range 60-92), cytogenetic risk group according to ELN recommendations (high, 26%; intermediate, 72%; low, 2%; p=0.35), HCT-CI score <3 (p=0.50), but significantly more patients with ECOG performance status >1 (p<0.001) were in the BSC group, however, without difference between the treatment-groups AZA, DAC, LDAC (p=0.76). Patients with a NPM1 mutation were more frequently (p<0.001) found in the BSC (23%) and the LDAC (22%) group compared to AZA (5%) and DAC (10%). Overall, FLT3-ITD and FLT3-TKD were detected rarely and mutually exclusive (3% each) without a difference between the groups (p=0.87, p=0.89). Significantly (p<0.001) higher white blood counts (WBC) at diagnosis were present in the BSC (median, 27/nl) and LDAC (median, 29.6/nl) compared to AZA (median, 3.5/nl) and DAC (median, 5.0/nl), no differences between groups were present for platelets (p=0.97) and hemoglobin (p=0.60). Median, one-year and two-year survival according to the 4 groups (BSC, AZA, DAC, LDAC) are given in the table.
| BSC | AZA | DAC | LDAC | |
| median survival (months) | 0.9 | 9.7 | 10.1 | 3.5 |
| one-year survival | 12% | 45% | 46% | 29% |
| two-years survival | 2% | 13% | 8% | 14% |
In a Cox regression model including all patients receiving therapy (AZA, DAC, LDAC), overall survival was significantly influenced by cytogenetic high-risk category (HR, 1.8; p=0.006), ECOG performance status <2 (HR, 0.5; p=0.0008), treatment (reference LDAC) with AZA (HR, 0.37; p=0.00003), DAC (HR, 0.38; p=0.00008), but not by NPM1 (p=0.72) and FLT3 (p=0.40) mutational status. In univariable comparisons, treatment with AZA and DAC resulted in a significantly better survival of patients with high-risk cytogenetics (p=0.001), normal cytogenetics (p=0.03), ECOG performance status <2 (p=0.0007), HCT-CI score <3 (p=0.0006) and low WBC (<4.0/nl).
Summary
In older patients with AML treatment with AZA or DAC is in the short-term perspective of one to two years superior to LDAC. However, results beyond 2 years are still dismal for all treatment options.
Keyword(s): AML, Cytarabine, Decitabine
Session topic: AML outcome and clinical trials
Abstract: S512
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:00 to 13.06.2015 16:15
Location: Room C2
Background
Comparative population-based outcome data in AML of older patients not fit for intensive chemotherapy are rare. Currently available treatment options outside clinical trials are best supportive care (BSC), decitabine (DAC), azacitidine (AZA), and low-dose cytarabine (LDAC).
Aims
To assess clinical outcome in patients older than 60 years not fit for intensive chemotherapy within the registry/molecular-screening trial AMLSG BiO (NCT01252485).
Methods
Between 2011 and 2014 a total of 2651 patients (median age 72 years, range 60- 94) have been registered. Molecular screening was performed within 48hours for NPM1 and FLT3 mutations as well as for the fusion-genes PML-RARA, RUNX1-RUNX1T1, MYH11-CBFβ. Treatment and outcome data were documented based on medical records and case record forms.
Results
Of the 2651 patients, n=1104 (42%) received intensive chemotherapy, n=88 (3%) AZA, n=162 (6%) DAC, n=250 (9%) LDAC, n=229 (9%) BSC, n=818 (31%) unknown. Of the 729 patients treated non-intensively n=176 (LDAC, n=134; DAC, n=40; AZA, n=1) were treated in clinical trials. Of the remaining 553 patients, the distribution according to treatment was n=116 LDAC, n=122 DAC, n=87 AZA and n=228 BSC. There was no difference in the age distribution between the groups BSC, AZA, DAC, LDAC (p=0.22, median 76 years, range 60-92), cytogenetic risk group according to ELN recommendations (high, 26%; intermediate, 72%; low, 2%; p=0.35), HCT-CI score <3 (p=0.50), but significantly more patients with ECOG performance status >1 (p<0.001) were in the BSC group, however, without difference between the treatment-groups AZA, DAC, LDAC (p=0.76). Patients with a NPM1 mutation were more frequently (p<0.001) found in the BSC (23%) and the LDAC (22%) group compared to AZA (5%) and DAC (10%). Overall, FLT3-ITD and FLT3-TKD were detected rarely and mutually exclusive (3% each) without a difference between the groups (p=0.87, p=0.89). Significantly (p<0.001) higher white blood counts (WBC) at diagnosis were present in the BSC (median, 27/nl) and LDAC (median, 29.6/nl) compared to AZA (median, 3.5/nl) and DAC (median, 5.0/nl), no differences between groups were present for platelets (p=0.97) and hemoglobin (p=0.60). Median, one-year and two-year survival according to the 4 groups (BSC, AZA, DAC, LDAC) are given in the table.
Summary
In older patients with AML treatment with AZA or DAC is in the short-term perspective of one to two years superior to LDAC. However, results beyond 2 years are still dismal for all treatment options.
Keyword(s): AML, Cytarabine, Decitabine
Session topic: AML outcome and clinical trials
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:00 to 13.06.2015 16:15
Location: Room C2
Background
Comparative population-based outcome data in AML of older patients not fit for intensive chemotherapy are rare. Currently available treatment options outside clinical trials are best supportive care (BSC), decitabine (DAC), azacitidine (AZA), and low-dose cytarabine (LDAC).
Aims
To assess clinical outcome in patients older than 60 years not fit for intensive chemotherapy within the registry/molecular-screening trial AMLSG BiO (NCT01252485).
Methods
Between 2011 and 2014 a total of 2651 patients (median age 72 years, range 60- 94) have been registered. Molecular screening was performed within 48hours for NPM1 and FLT3 mutations as well as for the fusion-genes PML-RARA, RUNX1-RUNX1T1, MYH11-CBFβ. Treatment and outcome data were documented based on medical records and case record forms.
Results
Of the 2651 patients, n=1104 (42%) received intensive chemotherapy, n=88 (3%) AZA, n=162 (6%) DAC, n=250 (9%) LDAC, n=229 (9%) BSC, n=818 (31%) unknown. Of the 729 patients treated non-intensively n=176 (LDAC, n=134; DAC, n=40; AZA, n=1) were treated in clinical trials. Of the remaining 553 patients, the distribution according to treatment was n=116 LDAC, n=122 DAC, n=87 AZA and n=228 BSC. There was no difference in the age distribution between the groups BSC, AZA, DAC, LDAC (p=0.22, median 76 years, range 60-92), cytogenetic risk group according to ELN recommendations (high, 26%; intermediate, 72%; low, 2%; p=0.35), HCT-CI score <3 (p=0.50), but significantly more patients with ECOG performance status >1 (p<0.001) were in the BSC group, however, without difference between the treatment-groups AZA, DAC, LDAC (p=0.76). Patients with a NPM1 mutation were more frequently (p<0.001) found in the BSC (23%) and the LDAC (22%) group compared to AZA (5%) and DAC (10%). Overall, FLT3-ITD and FLT3-TKD were detected rarely and mutually exclusive (3% each) without a difference between the groups (p=0.87, p=0.89). Significantly (p<0.001) higher white blood counts (WBC) at diagnosis were present in the BSC (median, 27/nl) and LDAC (median, 29.6/nl) compared to AZA (median, 3.5/nl) and DAC (median, 5.0/nl), no differences between groups were present for platelets (p=0.97) and hemoglobin (p=0.60). Median, one-year and two-year survival according to the 4 groups (BSC, AZA, DAC, LDAC) are given in the table.
| BSC | AZA | DAC | LDAC | |
| median survival (months) | 0.9 | 9.7 | 10.1 | 3.5 |
| one-year survival | 12% | 45% | 46% | 29% |
| two-years survival | 2% | 13% | 8% | 14% |
In a Cox regression model including all patients receiving therapy (AZA, DAC, LDAC), overall survival was significantly influenced by cytogenetic high-risk category (HR, 1.8; p=0.006), ECOG performance status <2 (HR, 0.5; p=0.0008), treatment (reference LDAC) with AZA (HR, 0.37; p=0.00003), DAC (HR, 0.38; p=0.00008), but not by NPM1 (p=0.72) and FLT3 (p=0.40) mutational status. In univariable comparisons, treatment with AZA and DAC resulted in a significantly better survival of patients with high-risk cytogenetics (p=0.001), normal cytogenetics (p=0.03), ECOG performance status <2 (p=0.0007), HCT-CI score <3 (p=0.0006) and low WBC (<4.0/nl).
Summary
In older patients with AML treatment with AZA or DAC is in the short-term perspective of one to two years superior to LDAC. However, results beyond 2 years are still dismal for all treatment options.
Keyword(s): AML, Cytarabine, Decitabine
Session topic: AML outcome and clinical trials
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