Contributions
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:30 to 13.06.2015 16:45
Location: Room C2
Background
In older patients (>60yrs) the UK NCRI AML16 trial compared two courses of DA vs DClo induction with or without gemtuzumab ozogamicin (GO). The benefit of the addition of GO has been reported (Burnett et al J Clin. Oncol 30(32);3924-3931, 2012).
Aims
Based on a feasibility study a schedule of Clofarabine 20mg/m2 d 1-5 was combined with Daunorubicin (Dauno) 50mg/m2 d 1-3 for two courses, and compared with Dauno 50mg/m2 d 1,3,5 + ara-C 100mg/m2 bid d 1-10 (course 1) or d 1-8 (course 2). Subsequently, patients with at least a partial remission (<15% marrow blasts) after course 1, and CR after course 2 were eligible to be randomised to one course of consolidation (Dauno 50mg/m2 days 1, 2 + ara-C 100mg/m2 bid days 1-5); patients in CR could be randomised to azacytidine maintenance or not.
Methods
From 8/2006-12/2009, 806 patients were randomised between DA and DClo, of whom 683 entered the GO randomisation. The median age was 67y (56-84); 72% had de novo, 17% secondary, and 11% high risk MDS; 4%, 73% and 23% had favourable, intermediate, poor risk cytogenetics; 14% were FLT3-ITD and 20% NPM1 mutant; 30%, 34%, 36% had good, standard, poor Wheatley risk. Following the two courses of induction, 263 patients were randomised to 2 vs 3 courses (138 from DA and 125 from DClo; 42% were Wheatley good risk, 37% standard risk, 21% poor risk). 274 were randomised to maintenance or not (137 from DA and 137 from DClo). The post induction interventions will be reported separately, but are taken into account in this assessment of induction treatments. Follow-up is complete to 1/1/2014 (median FU 66 months).
Results
In the DA vs DClo randomisation, the overall response rate (ORR) was 68% (CR 61%, CRi 7%) and 5-year OS 14%. The ORR was not different between DA: 71% (CR 64%, CRi 6%) and DClo 66% (CR 58%, CRi 8%), OR 1.26 (0.94-1.70) p=0.12, with 60 day all-cause mortality of 15% and 14% respectively. Remission rates after course 1 were higher with DA (54% vs 47%, OR 1.33 (1.01-1.76) p=0.04). There were no significant differences between DA and DClo at 5 years in RFS (14% vs 15%, HR 0.98 (0.82-1.18) p=0.9), CIR (78% vs 71%, HR 0.92 (0.76-1.12) p=0.4), death in CR (8% vs 14%, HR 1.50 (0.90-2.49) p=0.12), survival from CR (20% vs 22%, HR 0.96 (0.79-1.16) p=0.6), survival from relapse (4% vs 7%, HR 0.92 (0.75-1.13) p=0.4) or OS (15% vs 14%, HR 1.04 (0.89-1.21) p=0.6). The schedules were equi-toxic, and although neutrophil and platelet recovery was quicker in the DA arm in both courses DClo patients received significantly less transfusion support, days on antibiotics and hospitalisation. There was no evidence of interaction between the two induction randomisations, or between the DA vs DClo randomisation and any demographic feature. There was no evidence of interaction between the number of courses (3 vs 2) or receipt of maintenance or not. 135/410 patients in the clofarabine induction randomisation who achieved CR post course 1had information for MRD by immuno-flow analysis (Freeman S. et al. J Clin. Oncol. 31; 4123-4131, 2013), Of patients in morphological CR after the first induction course 48% of DA and 47% of DClo patients were MRD –ve which resulted in a survival of 25% and 37% respectively. For those who were in CR but were MRD +ve the survival was 14% for DA and 19% for DClo patients.
Summary
DA and DClo in induction give similar outcomes in older patients, with equivalent toxicity, and slightly lower resource usage on the DClo arm. Of patients in CR after course 1, as defined by immunoflow MRD +ve.
Acknowledgements: This study received research support from Genzyme and Cancer Research UK.
Keyword(s): Clinical trial, Clofarabine, Induction chemotherapy
Session topic: AML outcome and clinical trials
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:30 to 13.06.2015 16:45
Location: Room C2
Background
In older patients (>60yrs) the UK NCRI AML16 trial compared two courses of DA vs DClo induction with or without gemtuzumab ozogamicin (GO). The benefit of the addition of GO has been reported (Burnett et al J Clin. Oncol 30(32);3924-3931, 2012).
Aims
Based on a feasibility study a schedule of Clofarabine 20mg/m2 d 1-5 was combined with Daunorubicin (Dauno) 50mg/m2 d 1-3 for two courses, and compared with Dauno 50mg/m2 d 1,3,5 + ara-C 100mg/m2 bid d 1-10 (course 1) or d 1-8 (course 2). Subsequently, patients with at least a partial remission (<15% marrow blasts) after course 1, and CR after course 2 were eligible to be randomised to one course of consolidation (Dauno 50mg/m2 days 1, 2 + ara-C 100mg/m2 bid days 1-5); patients in CR could be randomised to azacytidine maintenance or not.
Methods
From 8/2006-12/2009, 806 patients were randomised between DA and DClo, of whom 683 entered the GO randomisation. The median age was 67y (56-84); 72% had de novo, 17% secondary, and 11% high risk MDS; 4%, 73% and 23% had favourable, intermediate, poor risk cytogenetics; 14% were FLT3-ITD and 20% NPM1 mutant; 30%, 34%, 36% had good, standard, poor Wheatley risk. Following the two courses of induction, 263 patients were randomised to 2 vs 3 courses (138 from DA and 125 from DClo; 42% were Wheatley good risk, 37% standard risk, 21% poor risk). 274 were randomised to maintenance or not (137 from DA and 137 from DClo). The post induction interventions will be reported separately, but are taken into account in this assessment of induction treatments. Follow-up is complete to 1/1/2014 (median FU 66 months).
Results
In the DA vs DClo randomisation, the overall response rate (ORR) was 68% (CR 61%, CRi 7%) and 5-year OS 14%. The ORR was not different between DA: 71% (CR 64%, CRi 6%) and DClo 66% (CR 58%, CRi 8%), OR 1.26 (0.94-1.70) p=0.12, with 60 day all-cause mortality of 15% and 14% respectively. Remission rates after course 1 were higher with DA (54% vs 47%, OR 1.33 (1.01-1.76) p=0.04). There were no significant differences between DA and DClo at 5 years in RFS (14% vs 15%, HR 0.98 (0.82-1.18) p=0.9), CIR (78% vs 71%, HR 0.92 (0.76-1.12) p=0.4), death in CR (8% vs 14%, HR 1.50 (0.90-2.49) p=0.12), survival from CR (20% vs 22%, HR 0.96 (0.79-1.16) p=0.6), survival from relapse (4% vs 7%, HR 0.92 (0.75-1.13) p=0.4) or OS (15% vs 14%, HR 1.04 (0.89-1.21) p=0.6). The schedules were equi-toxic, and although neutrophil and platelet recovery was quicker in the DA arm in both courses DClo patients received significantly less transfusion support, days on antibiotics and hospitalisation. There was no evidence of interaction between the two induction randomisations, or between the DA vs DClo randomisation and any demographic feature. There was no evidence of interaction between the number of courses (3 vs 2) or receipt of maintenance or not. 135/410 patients in the clofarabine induction randomisation who achieved CR post course 1had information for MRD by immuno-flow analysis (Freeman S. et al. J Clin. Oncol. 31; 4123-4131, 2013), Of patients in morphological CR after the first induction course 48% of DA and 47% of DClo patients were MRD –ve which resulted in a survival of 25% and 37% respectively. For those who were in CR but were MRD +ve the survival was 14% for DA and 19% for DClo patients.
Summary
DA and DClo in induction give similar outcomes in older patients, with equivalent toxicity, and slightly lower resource usage on the DClo arm. Of patients in CR after course 1, as defined by immunoflow MRD +ve.
Acknowledgements: This study received research support from Genzyme and Cancer Research UK.
Keyword(s): Clinical trial, Clofarabine, Induction chemotherapy
Session topic: AML outcome and clinical trials