FINAL RESULTS OF THE CETLAM LAM-2003 TRIAL FOR THE TREATMENT OF PRIMARY AML UP TO THE AGE OF 70
(Abstract release date: 05/18/17)
EHA Library. Garrido A. 06/25/17; 182077; S790
Ana Garrido
Contributions
Contributions
Abstract
Abstract: S790
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30
Location: Room N101
Background
AML is a heterogeneous disease based on genetic characteristics with impact on prognosis. So, it becomes necessary to treat patients according to risk-adapted therapies.
Aims
To analyze the results of intensive induction and post-remission treatment in 868 patients with the novo AML enrolled into the CETLAM-03 trial between 2003 and 2012 with a prolonged follow-up (results reported at 10 years).
Methods
Patients received 1 or 2 induction chemotherapy courses of IDICE-G (idarubicin, intermediate cytarabine (IDC), VP-16 and priming with G-CSF) followed by mitoxantrone and IDC as consolidation therapy. Further treatment was assigned according to the CETLAM risk groups as follows: Favorable risk (FR) defined as favorable cytogenetics according to MRC: autologous stem cell transplantation (ASCT) if leukocyte index [LI=leucocytes x (BM blasts/100)] > 20 or high dose cytarabine (HDAC) (one course) if LI <20. Intermediate risk (IR), defined as patients in CR after a single induction course, <50x10E9/l white blood cells at diagnosis, normal karyotype and absence of FLT3 internal tandem duplication (FlT3-ITDwt) and no MLL rearrangement: ASCT . Adverse risk (AR), patients not included in FP or IP: ASCT or allogeneic stem cell transplantation (allo-SCT) depending on donor availability (HLA-identical sibling or unrelated donor if high risk of relapse).
Results
There were enrolled 868 patients. Median age was 53 years-old (16-70). According to MRC cytogenetics, available in 802 patients, 99 belonged to the favorable (12%), 581 (73%) to the intermediate and 122 (15%) to the adverse groups. 66 patients with no metaphases. FLT3-ITD was present in 128 patients with normal karyotype (36%). Four patients died before treatment and 864 patients received induction therapy. 77% of patients achieved a CR (88% with a single course), 11% were refractory and 12% died during induction. CR rate was 92% in CBF leukemia, 91% in NPM1 mutation without FLT3-ITD, 77% in intermediate cytogenetic and no mutations, 74% if FLT3-ITD, 70% in adverse cytogenetics and 62% if monosomal karyotype was present (p<0.001). The multivariate analysis showed that mutational status (adverse cytogenetics, FLT3-ITD and absence of NPM1 mutation) had an adverse impact on CR achievement. Overall survival (OS), event free survival (EFS) and cumulative incidence of relapse (CIR) of the whole series at 10 years were: 36±2%, 29±2% and 44±5% respectively. Post-remission results of OS, EFS and CIR according to the different CETLAM risk groups at 10 years follow up were: FR (n=85, 14%): 85±4%, 70±6% and 22±1%; IR (n=99, 17%): 64±6%, 51±5% and 47±2%; AR (n=417, 69%): 41±3%, 33±3% and 52±16% respectively. In FR there were no differences in OS, EFS and CIR depending if intention to treat was HDAC or ASCT. In AR statistical differences were observed at 10 years in EFS and CIR when comparing ASCT vs allo-SCT (27±4% vs 39±4%, p=0.026 and 66±6% vs 39±1%, p<0.001). In IR intention to treat was ASCT, but in 21% mobilization failed and most of them received HDAC. Forty-nine patients received an ASCT and 21 relapsed, 9 of them were rescued with an allo-SCT.
Conclusion
In this large cooperative experience CR rate was above 75%, in most cases after a single course. In patients with favorable MRC cytogenetics, the adverse impact of high LI observed in our previous protocol was abrogated with autologous transplantation. In IR group, a remarkable proportion of patients allocated to ASCT had mobilization failure. In HR group, allo-SCT improves the outcome compared to ASCT. In our experience, molecular characterization and MRD studies are helpful to decide post-remission therapy
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Molecular markers, Cytogenetics, chemotherapy, AML
Abstract: S790
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30
Location: Room N101
Background
AML is a heterogeneous disease based on genetic characteristics with impact on prognosis. So, it becomes necessary to treat patients according to risk-adapted therapies.
Aims
To analyze the results of intensive induction and post-remission treatment in 868 patients with the novo AML enrolled into the CETLAM-03 trial between 2003 and 2012 with a prolonged follow-up (results reported at 10 years).
Methods
Patients received 1 or 2 induction chemotherapy courses of IDICE-G (idarubicin, intermediate cytarabine (IDC), VP-16 and priming with G-CSF) followed by mitoxantrone and IDC as consolidation therapy. Further treatment was assigned according to the CETLAM risk groups as follows: Favorable risk (FR) defined as favorable cytogenetics according to MRC: autologous stem cell transplantation (ASCT) if leukocyte index [LI=leucocytes x (BM blasts/100)] > 20 or high dose cytarabine (HDAC) (one course) if LI <20. Intermediate risk (IR), defined as patients in CR after a single induction course, <50x10E9/l white blood cells at diagnosis, normal karyotype and absence of FLT3 internal tandem duplication (FlT3-ITDwt) and no MLL rearrangement: ASCT . Adverse risk (AR), patients not included in FP or IP: ASCT or allogeneic stem cell transplantation (allo-SCT) depending on donor availability (HLA-identical sibling or unrelated donor if high risk of relapse).
Results
There were enrolled 868 patients. Median age was 53 years-old (16-70). According to MRC cytogenetics, available in 802 patients, 99 belonged to the favorable (12%), 581 (73%) to the intermediate and 122 (15%) to the adverse groups. 66 patients with no metaphases. FLT3-ITD was present in 128 patients with normal karyotype (36%). Four patients died before treatment and 864 patients received induction therapy. 77% of patients achieved a CR (88% with a single course), 11% were refractory and 12% died during induction. CR rate was 92% in CBF leukemia, 91% in NPM1 mutation without FLT3-ITD, 77% in intermediate cytogenetic and no mutations, 74% if FLT3-ITD, 70% in adverse cytogenetics and 62% if monosomal karyotype was present (p<0.001). The multivariate analysis showed that mutational status (adverse cytogenetics, FLT3-ITD and absence of NPM1 mutation) had an adverse impact on CR achievement. Overall survival (OS), event free survival (EFS) and cumulative incidence of relapse (CIR) of the whole series at 10 years were: 36±2%, 29±2% and 44±5% respectively. Post-remission results of OS, EFS and CIR according to the different CETLAM risk groups at 10 years follow up were: FR (n=85, 14%): 85±4%, 70±6% and 22±1%; IR (n=99, 17%): 64±6%, 51±5% and 47±2%; AR (n=417, 69%): 41±3%, 33±3% and 52±16% respectively. In FR there were no differences in OS, EFS and CIR depending if intention to treat was HDAC or ASCT. In AR statistical differences were observed at 10 years in EFS and CIR when comparing ASCT vs allo-SCT (27±4% vs 39±4%, p=0.026 and 66±6% vs 39±1%, p<0.001). In IR intention to treat was ASCT, but in 21% mobilization failed and most of them received HDAC. Forty-nine patients received an ASCT and 21 relapsed, 9 of them were rescued with an allo-SCT.
Conclusion
In this large cooperative experience CR rate was above 75%, in most cases after a single course. In patients with favorable MRC cytogenetics, the adverse impact of high LI observed in our previous protocol was abrogated with autologous transplantation. In IR group, a remarkable proportion of patients allocated to ASCT had mobilization failure. In HR group, allo-SCT improves the outcome compared to ASCT. In our experience, molecular characterization and MRD studies are helpful to decide post-remission therapy
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Molecular markers, Cytogenetics, chemotherapy, AML
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