RISK ADAPTED THERAPY FOR ACUTE MYELOID LEUKEMIA (AML) BASED ON GENETIC DATA AND MINIMAL RESIDUAL DISEASE: RESULTS OF THE AML12 TRIAL OF THE CETLAM GROUP IN ADULTS UP TO THE AGE OF 70 YEARS.
(Abstract release date: 05/19/16)
EHA Library. Sierra J. 06/11/16; 135240; S484
Prof. Dr. Jorge Sierra
Contributions
Contributions
Abstract
Abstract: S484
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A2
Background
Refinement of the AML risk stratification based on genetic data (cytogenetics and molecular characteristics) and minimal residual disease (MRD) assessment may optimize the post-remission allocation to consolidation chemotherapy only or hematopoietic cell transplantation (HCT).
Aims
To evaluate the feasibility and results of an ongoing prospective phase II trial of intensive chemotherapy followed or not by HCT depending on genetics of AML and levels of MRD after consolidation.
Methods
Patients 18 to 70 years old with primary AML treated at 15 academic hospitals between February 2012 and November 2015 were enrolled in the trial. The number of patients included and the outcomes will be updated on May 1, 2016. Induction consisted of idarubicin 12 mg/m2 days 1-2-3 as intravenous bolus and cytarabine 200 mg/m2 as continuous infusion days 1 to 7. Consolidation courses were the high-dose cytarabine schedule of the CALGB with reduction of cytarabine from 3 g/m2 to 1.5 g/m2 in patients older than 60 years. The number of consolidation courses was based on AML risk allocation: three in the low-risk category (CBF, NPM1mut/FLT3-ITDwild or ratio<0.5, CEBPA biallelic mutation, all of them with low MRD after consolidation (by flow cytometry and/or quantitative PCR of the specific transcripts); two in the intermediate risk category (intermediate cytogenetics without favorable or unfavorable mutations (these patients subsequently received an autologous or allogeneic transplantation depending on MRD levels and availability of an HLA matched donor); and one consolidation followed by mandatory allogeneic transplantation from any stem cell source available (identical sibling, unrelated, cord blood, haploidentical ) in the high-risk group (adverse genetics and/or MRD persistence on high levels).
Results
In 372 patients enrolled so far, the median age (range) was 55 (18-70) years and 53% were male. MRC cytogenetic distribution was: CBF AML 12%, intermediate-risk 66% and poor risk 22%. FLT3-ITD was detected in 22% of 348 cases studied (29% in intermediate risk cytogenetics) group and NPM1 mutation was evident in 57% of patients with a NK.Complete remission (CR) rate in 365 evaluable patients was 74% (n=272), Induction death occurred in 9% and 19% in patients up to and above 60 years, respectively; 10% of patients had refractory leukemia in the two age categories. Two hundred forty patients completed the consolidation phase and were risk allocated; 104 (43%) to the genetics-MRD favorable category, 73 (30%) to the intermediate and 65 (27%) to the high-risk group; in the latter, 80% of patients received an allogeneic HCT. Median follow-up of the surviving patients is 16 months. Overall survival (OS) of the whole series was 47+3% at 30 months; disease-free survivals at that time point were 74+5% in the favorable risk group, 44+5% in the intermediate and 29+7% in the in the high-risk group (Figure), due to significantly difference in the relapse incidence (23%, 41% and 56%, respectively). Remarkably, we confirmed our previous finding that patients with intermediate-risk MRC cytogenetics with NPM1 mutation and FLT3-ITDwild had comparable outcomes to those with NPM1 mutation and an allelic ratio below 0.5.
Conclusion
Risk adapted therapy for primary AML based on genetics and MRD is feasible in a cooperative group setting. The proportion of patients in whom the risks of an allogeneic HCT in first CR may be avoided is higher than 40% when considering not only cytogenetics but also molecular and MRD information. Allogeneic HCT in high-risk patients was feasible in most instances but further approaches to decrease relapses such as novel agents and immune therapies are needed.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Minimal residual disease (MRD), Risk factor, Therapy
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A2
Background
Refinement of the AML risk stratification based on genetic data (cytogenetics and molecular characteristics) and minimal residual disease (MRD) assessment may optimize the post-remission allocation to consolidation chemotherapy only or hematopoietic cell transplantation (HCT).
Aims
To evaluate the feasibility and results of an ongoing prospective phase II trial of intensive chemotherapy followed or not by HCT depending on genetics of AML and levels of MRD after consolidation.
Methods
Patients 18 to 70 years old with primary AML treated at 15 academic hospitals between February 2012 and November 2015 were enrolled in the trial. The number of patients included and the outcomes will be updated on May 1, 2016. Induction consisted of idarubicin 12 mg/m2 days 1-2-3 as intravenous bolus and cytarabine 200 mg/m2 as continuous infusion days 1 to 7. Consolidation courses were the high-dose cytarabine schedule of the CALGB with reduction of cytarabine from 3 g/m2 to 1.5 g/m2 in patients older than 60 years. The number of consolidation courses was based on AML risk allocation: three in the low-risk category (CBF, NPM1mut/FLT3-ITDwild or ratio<0.5, CEBPA biallelic mutation, all of them with low MRD after consolidation (by flow cytometry and/or quantitative PCR of the specific transcripts); two in the intermediate risk category (intermediate cytogenetics without favorable or unfavorable mutations (these patients subsequently received an autologous or allogeneic transplantation depending on MRD levels and availability of an HLA matched donor); and one consolidation followed by mandatory allogeneic transplantation from any stem cell source available (identical sibling, unrelated, cord blood, haploidentical ) in the high-risk group (adverse genetics and/or MRD persistence on high levels).
Results
In 372 patients enrolled so far, the median age (range) was 55 (18-70) years and 53% were male. MRC cytogenetic distribution was: CBF AML 12%, intermediate-risk 66% and poor risk 22%. FLT3-ITD was detected in 22% of 348 cases studied (29% in intermediate risk cytogenetics) group and NPM1 mutation was evident in 57% of patients with a NK.Complete remission (CR) rate in 365 evaluable patients was 74% (n=272), Induction death occurred in 9% and 19% in patients up to and above 60 years, respectively; 10% of patients had refractory leukemia in the two age categories. Two hundred forty patients completed the consolidation phase and were risk allocated; 104 (43%) to the genetics-MRD favorable category, 73 (30%) to the intermediate and 65 (27%) to the high-risk group; in the latter, 80% of patients received an allogeneic HCT. Median follow-up of the surviving patients is 16 months. Overall survival (OS) of the whole series was 47+3% at 30 months; disease-free survivals at that time point were 74+5% in the favorable risk group, 44+5% in the intermediate and 29+7% in the in the high-risk group (Figure), due to significantly difference in the relapse incidence (23%, 41% and 56%, respectively). Remarkably, we confirmed our previous finding that patients with intermediate-risk MRC cytogenetics with NPM1 mutation and FLT3-ITDwild had comparable outcomes to those with NPM1 mutation and an allelic ratio below 0.5.
Conclusion
Risk adapted therapy for primary AML based on genetics and MRD is feasible in a cooperative group setting. The proportion of patients in whom the risks of an allogeneic HCT in first CR may be avoided is higher than 40% when considering not only cytogenetics but also molecular and MRD information. Allogeneic HCT in high-risk patients was feasible in most instances but further approaches to decrease relapses such as novel agents and immune therapies are needed.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Minimal residual disease (MRD), Risk factor, Therapy
Abstract: S484
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A2
Background
Refinement of the AML risk stratification based on genetic data (cytogenetics and molecular characteristics) and minimal residual disease (MRD) assessment may optimize the post-remission allocation to consolidation chemotherapy only or hematopoietic cell transplantation (HCT).
Aims
To evaluate the feasibility and results of an ongoing prospective phase II trial of intensive chemotherapy followed or not by HCT depending on genetics of AML and levels of MRD after consolidation.
Methods
Patients 18 to 70 years old with primary AML treated at 15 academic hospitals between February 2012 and November 2015 were enrolled in the trial. The number of patients included and the outcomes will be updated on May 1, 2016. Induction consisted of idarubicin 12 mg/m2 days 1-2-3 as intravenous bolus and cytarabine 200 mg/m2 as continuous infusion days 1 to 7. Consolidation courses were the high-dose cytarabine schedule of the CALGB with reduction of cytarabine from 3 g/m2 to 1.5 g/m2 in patients older than 60 years. The number of consolidation courses was based on AML risk allocation: three in the low-risk category (CBF, NPM1mut/FLT3-ITDwild or ratio<0.5, CEBPA biallelic mutation, all of them with low MRD after consolidation (by flow cytometry and/or quantitative PCR of the specific transcripts); two in the intermediate risk category (intermediate cytogenetics without favorable or unfavorable mutations (these patients subsequently received an autologous or allogeneic transplantation depending on MRD levels and availability of an HLA matched donor); and one consolidation followed by mandatory allogeneic transplantation from any stem cell source available (identical sibling, unrelated, cord blood, haploidentical ) in the high-risk group (adverse genetics and/or MRD persistence on high levels).
Results
In 372 patients enrolled so far, the median age (range) was 55 (18-70) years and 53% were male. MRC cytogenetic distribution was: CBF AML 12%, intermediate-risk 66% and poor risk 22%. FLT3-ITD was detected in 22% of 348 cases studied (29% in intermediate risk cytogenetics) group and NPM1 mutation was evident in 57% of patients with a NK.Complete remission (CR) rate in 365 evaluable patients was 74% (n=272), Induction death occurred in 9% and 19% in patients up to and above 60 years, respectively; 10% of patients had refractory leukemia in the two age categories. Two hundred forty patients completed the consolidation phase and were risk allocated; 104 (43%) to the genetics-MRD favorable category, 73 (30%) to the intermediate and 65 (27%) to the high-risk group; in the latter, 80% of patients received an allogeneic HCT. Median follow-up of the surviving patients is 16 months. Overall survival (OS) of the whole series was 47+3% at 30 months; disease-free survivals at that time point were 74+5% in the favorable risk group, 44+5% in the intermediate and 29+7% in the in the high-risk group (Figure), due to significantly difference in the relapse incidence (23%, 41% and 56%, respectively). Remarkably, we confirmed our previous finding that patients with intermediate-risk MRC cytogenetics with NPM1 mutation and FLT3-ITDwild had comparable outcomes to those with NPM1 mutation and an allelic ratio below 0.5.
Conclusion
Risk adapted therapy for primary AML based on genetics and MRD is feasible in a cooperative group setting. The proportion of patients in whom the risks of an allogeneic HCT in first CR may be avoided is higher than 40% when considering not only cytogenetics but also molecular and MRD information. Allogeneic HCT in high-risk patients was feasible in most instances but further approaches to decrease relapses such as novel agents and immune therapies are needed.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Minimal residual disease (MRD), Risk factor, Therapy
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall A2
Background
Refinement of the AML risk stratification based on genetic data (cytogenetics and molecular characteristics) and minimal residual disease (MRD) assessment may optimize the post-remission allocation to consolidation chemotherapy only or hematopoietic cell transplantation (HCT).
Aims
To evaluate the feasibility and results of an ongoing prospective phase II trial of intensive chemotherapy followed or not by HCT depending on genetics of AML and levels of MRD after consolidation.
Methods
Patients 18 to 70 years old with primary AML treated at 15 academic hospitals between February 2012 and November 2015 were enrolled in the trial. The number of patients included and the outcomes will be updated on May 1, 2016. Induction consisted of idarubicin 12 mg/m2 days 1-2-3 as intravenous bolus and cytarabine 200 mg/m2 as continuous infusion days 1 to 7. Consolidation courses were the high-dose cytarabine schedule of the CALGB with reduction of cytarabine from 3 g/m2 to 1.5 g/m2 in patients older than 60 years. The number of consolidation courses was based on AML risk allocation: three in the low-risk category (CBF, NPM1mut/FLT3-ITDwild or ratio<0.5, CEBPA biallelic mutation, all of them with low MRD after consolidation (by flow cytometry and/or quantitative PCR of the specific transcripts); two in the intermediate risk category (intermediate cytogenetics without favorable or unfavorable mutations (these patients subsequently received an autologous or allogeneic transplantation depending on MRD levels and availability of an HLA matched donor); and one consolidation followed by mandatory allogeneic transplantation from any stem cell source available (identical sibling, unrelated, cord blood, haploidentical ) in the high-risk group (adverse genetics and/or MRD persistence on high levels).
Results
In 372 patients enrolled so far, the median age (range) was 55 (18-70) years and 53% were male. MRC cytogenetic distribution was: CBF AML 12%, intermediate-risk 66% and poor risk 22%. FLT3-ITD was detected in 22% of 348 cases studied (29% in intermediate risk cytogenetics) group and NPM1 mutation was evident in 57% of patients with a NK.Complete remission (CR) rate in 365 evaluable patients was 74% (n=272), Induction death occurred in 9% and 19% in patients up to and above 60 years, respectively; 10% of patients had refractory leukemia in the two age categories. Two hundred forty patients completed the consolidation phase and were risk allocated; 104 (43%) to the genetics-MRD favorable category, 73 (30%) to the intermediate and 65 (27%) to the high-risk group; in the latter, 80% of patients received an allogeneic HCT. Median follow-up of the surviving patients is 16 months. Overall survival (OS) of the whole series was 47+3% at 30 months; disease-free survivals at that time point were 74+5% in the favorable risk group, 44+5% in the intermediate and 29+7% in the in the high-risk group (Figure), due to significantly difference in the relapse incidence (23%, 41% and 56%, respectively). Remarkably, we confirmed our previous finding that patients with intermediate-risk MRC cytogenetics with NPM1 mutation and FLT3-ITDwild had comparable outcomes to those with NPM1 mutation and an allelic ratio below 0.5.
Conclusion
Risk adapted therapy for primary AML based on genetics and MRD is feasible in a cooperative group setting. The proportion of patients in whom the risks of an allogeneic HCT in first CR may be avoided is higher than 40% when considering not only cytogenetics but also molecular and MRD information. Allogeneic HCT in high-risk patients was feasible in most instances but further approaches to decrease relapses such as novel agents and immune therapies are needed.
Session topic: Standard Treatment Results in AML
Keyword(s): AML, Minimal residual disease (MRD), Risk factor, Therapy
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