SEQUENTIAL HIGH-DOSE CYTARABINE PLUS IDARUBICIN IMPROVES REMISSION RATE AND SURVIVAL DURATION IN ADULT ACUTE MYELOGENOUS LEUKEMIA (AML): RANDOMIZED TRIAL OF THE NORTHERN ITALY LEUKEMIA GROUP (NILG)
(Abstract release date: 05/19/16)
EHA Library. Bassan R. 06/11/16; 135241; S485
Dr. Renato Bassan
Contributions
Contributions
Abstract
Abstract: S485
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Hall A2
Background
AML is curable in the fraction of patients who achieve complete remission (CR) and do not relapse following consolidation or allogeneic stem cell transplantation (ASCT). Therefore new strategies are continuously developed to overcome the risk of primary resistant or recurrent disease.
Aims
In NILG trial 02/06 [ClinicalTrials.gov Identifier: NCT00495287]a sequential high-dose (SHD) regimen was compared to standard induction, having CR rate as primary study objective. CR patients were eligible to risk-specific treatment.
Methods
Study patients were stratified by age 60 years and randomized to ICE (idarubicin 12 mg/m2/d iv. dd1-3, cytarabine 100 mg/m2/bd iv. dd 1-7, etoposide 100 mg/m2/d iv. dd1-5) or SHD (cytarabine 2 g [1 g if age >65]/m2/bd iv. dd 1-2 and 8-9, idarubicin 18 mg/m2/d iv. dd 3 and 10), plus G-CSF from d11. Postremission consolidation consisted of IC (cycle 2), intermediate-dose cytarabine 1 g/m2/bd iv. dd 1-4, with harvest of CD34+ blood stem cells (cycle 3), and allogeneic SCT if high-risk or second randomization to BUCY2-conditioned autograft or repetitive HD cycles (cytarabine 2 g/m2/bd iv. dd 1-5 and idarubicin 8 mg/m2/d dd 1-2, cycles 4-6) supported by 1-2 x106/kg CD34+ cells. The high-risk class was defined by cytogenetics, selected risk factors in intermediate/normal cytogenetic risk group (FLT3 ITD+, WBC >50, minimally differentiated/megakaryo-/erythro-blastic,secondary or MDS-related AML), and late CR. Results were analyzed by treatment intention and, to detect late survival differences, compared using the Kaplan-Meier estimate with weighted log-rank tests according to Fleming and Harrington.
Results
Between 2006-2012, 572 patients were enrolled (median age 52 years, range 16-73; 74% high-risk; 286 with comparable characteristics in each arm). After induction course, CR rate was 69.2% in ICE arm and 81.5% in SHD arm (P .001), due to lower resistance rate (25.2% vs 11.2%, P <.0001) without increased mortality (5.6% vs 7.3%, P .39). The benefit was confirmed in high-risk AML (n=201 vs 218: CR 64.2% vs 77.6%; P .002) and in patients aged ≤60 years with de novo AML (n=190 vs 189: CR 74.2% vs 86.2%; P .003). Overall CR rate after cycle 2/other salvage was 82.5% vs 86.0% (P .25). SHD increased the time to neutrophil/platelet recovery (P <.0001), the risk of infections (bacterial, P .0001; fungal, P .003) and hepatic, metabolic and cutaneous toxicity (P <.05), and was associated with longer intercycle intervals (P<.0001), lower feasibility of cycle 3 (P <.0001) and poorer stem cell mobilization (n=123 vs 93). One-hundred ninety-three patients (41%) had an allograft in CR1 (175 high-risk [96 in ICE arm and 79 in HDS arm] and 18 standard-risk [6 in ICE arm and 12 in HDS arm]). Median and 5-year overall survival (OS) were 2.14 years and 38% in ICE arm compared to 4.51 years and 48% in SHD arm (P .0125), improving sensibly in the standard-risk subset (5-year OS 55% vs 72%, P .0068) and patients aged ≤60 years with de novo AML (5-year OS 43% vs 58%; P .0026). Median and 5-year DFS were 1.48 years and 36% compared to 3.41 years and 48% (P .0030), again improving in the standard-risk subset (5-year DFS 40% vs 64%; P .0064) and patients aged ≤60 years with de novo AML (5-year DFS 38% vs 54%; P .0023).
Conclusion
The current SHD schedule, albeit proving more toxic than standard ICE did not increase the risk of induction death and improved the CR rate and 5-year OS and DFS results, particularly in patients with standard-risk AML and aged ≤60 years with de novo AML.
Session topic: Standard Treatment Results in AML
Keyword(s): Acute myeloid leukemia, Adult, High dose therapy, Randomized
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Hall A2
Background
AML is curable in the fraction of patients who achieve complete remission (CR) and do not relapse following consolidation or allogeneic stem cell transplantation (ASCT). Therefore new strategies are continuously developed to overcome the risk of primary resistant or recurrent disease.
Aims
In NILG trial 02/06 [ClinicalTrials.gov Identifier: NCT00495287]a sequential high-dose (SHD) regimen was compared to standard induction, having CR rate as primary study objective. CR patients were eligible to risk-specific treatment.
Methods
Study patients were stratified by age 60 years and randomized to ICE (idarubicin 12 mg/m2/d iv. dd1-3, cytarabine 100 mg/m2/bd iv. dd 1-7, etoposide 100 mg/m2/d iv. dd1-5) or SHD (cytarabine 2 g [1 g if age >65]/m2/bd iv. dd 1-2 and 8-9, idarubicin 18 mg/m2/d iv. dd 3 and 10), plus G-CSF from d11. Postremission consolidation consisted of IC (cycle 2), intermediate-dose cytarabine 1 g/m2/bd iv. dd 1-4, with harvest of CD34+ blood stem cells (cycle 3), and allogeneic SCT if high-risk or second randomization to BUCY2-conditioned autograft or repetitive HD cycles (cytarabine 2 g/m2/bd iv. dd 1-5 and idarubicin 8 mg/m2/d dd 1-2, cycles 4-6) supported by 1-2 x106/kg CD34+ cells. The high-risk class was defined by cytogenetics, selected risk factors in intermediate/normal cytogenetic risk group (FLT3 ITD+, WBC >50, minimally differentiated/megakaryo-/erythro-blastic,secondary or MDS-related AML), and late CR. Results were analyzed by treatment intention and, to detect late survival differences, compared using the Kaplan-Meier estimate with weighted log-rank tests according to Fleming and Harrington.
Results
Between 2006-2012, 572 patients were enrolled (median age 52 years, range 16-73; 74% high-risk; 286 with comparable characteristics in each arm). After induction course, CR rate was 69.2% in ICE arm and 81.5% in SHD arm (P .001), due to lower resistance rate (25.2% vs 11.2%, P <.0001) without increased mortality (5.6% vs 7.3%, P .39). The benefit was confirmed in high-risk AML (n=201 vs 218: CR 64.2% vs 77.6%; P .002) and in patients aged ≤60 years with de novo AML (n=190 vs 189: CR 74.2% vs 86.2%; P .003). Overall CR rate after cycle 2/other salvage was 82.5% vs 86.0% (P .25). SHD increased the time to neutrophil/platelet recovery (P <.0001), the risk of infections (bacterial, P .0001; fungal, P .003) and hepatic, metabolic and cutaneous toxicity (P <.05), and was associated with longer intercycle intervals (P<.0001), lower feasibility of cycle 3 (P <.0001) and poorer stem cell mobilization (n=123 vs 93). One-hundred ninety-three patients (41%) had an allograft in CR1 (175 high-risk [96 in ICE arm and 79 in HDS arm] and 18 standard-risk [6 in ICE arm and 12 in HDS arm]). Median and 5-year overall survival (OS) were 2.14 years and 38% in ICE arm compared to 4.51 years and 48% in SHD arm (P .0125), improving sensibly in the standard-risk subset (5-year OS 55% vs 72%, P .0068) and patients aged ≤60 years with de novo AML (5-year OS 43% vs 58%; P .0026). Median and 5-year DFS were 1.48 years and 36% compared to 3.41 years and 48% (P .0030), again improving in the standard-risk subset (5-year DFS 40% vs 64%; P .0064) and patients aged ≤60 years with de novo AML (5-year DFS 38% vs 54%; P .0023).
Conclusion
The current SHD schedule, albeit proving more toxic than standard ICE did not increase the risk of induction death and improved the CR rate and 5-year OS and DFS results, particularly in patients with standard-risk AML and aged ≤60 years with de novo AML.
Session topic: Standard Treatment Results in AML
Keyword(s): Acute myeloid leukemia, Adult, High dose therapy, Randomized
Abstract: S485
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Hall A2
Background
AML is curable in the fraction of patients who achieve complete remission (CR) and do not relapse following consolidation or allogeneic stem cell transplantation (ASCT). Therefore new strategies are continuously developed to overcome the risk of primary resistant or recurrent disease.
Aims
In NILG trial 02/06 [ClinicalTrials.gov Identifier: NCT00495287]a sequential high-dose (SHD) regimen was compared to standard induction, having CR rate as primary study objective. CR patients were eligible to risk-specific treatment.
Methods
Study patients were stratified by age 60 years and randomized to ICE (idarubicin 12 mg/m2/d iv. dd1-3, cytarabine 100 mg/m2/bd iv. dd 1-7, etoposide 100 mg/m2/d iv. dd1-5) or SHD (cytarabine 2 g [1 g if age >65]/m2/bd iv. dd 1-2 and 8-9, idarubicin 18 mg/m2/d iv. dd 3 and 10), plus G-CSF from d11. Postremission consolidation consisted of IC (cycle 2), intermediate-dose cytarabine 1 g/m2/bd iv. dd 1-4, with harvest of CD34+ blood stem cells (cycle 3), and allogeneic SCT if high-risk or second randomization to BUCY2-conditioned autograft or repetitive HD cycles (cytarabine 2 g/m2/bd iv. dd 1-5 and idarubicin 8 mg/m2/d dd 1-2, cycles 4-6) supported by 1-2 x106/kg CD34+ cells. The high-risk class was defined by cytogenetics, selected risk factors in intermediate/normal cytogenetic risk group (FLT3 ITD+, WBC >50, minimally differentiated/megakaryo-/erythro-blastic,secondary or MDS-related AML), and late CR. Results were analyzed by treatment intention and, to detect late survival differences, compared using the Kaplan-Meier estimate with weighted log-rank tests according to Fleming and Harrington.
Results
Between 2006-2012, 572 patients were enrolled (median age 52 years, range 16-73; 74% high-risk; 286 with comparable characteristics in each arm). After induction course, CR rate was 69.2% in ICE arm and 81.5% in SHD arm (P .001), due to lower resistance rate (25.2% vs 11.2%, P <.0001) without increased mortality (5.6% vs 7.3%, P .39). The benefit was confirmed in high-risk AML (n=201 vs 218: CR 64.2% vs 77.6%; P .002) and in patients aged ≤60 years with de novo AML (n=190 vs 189: CR 74.2% vs 86.2%; P .003). Overall CR rate after cycle 2/other salvage was 82.5% vs 86.0% (P .25). SHD increased the time to neutrophil/platelet recovery (P <.0001), the risk of infections (bacterial, P .0001; fungal, P .003) and hepatic, metabolic and cutaneous toxicity (P <.05), and was associated with longer intercycle intervals (P<.0001), lower feasibility of cycle 3 (P <.0001) and poorer stem cell mobilization (n=123 vs 93). One-hundred ninety-three patients (41%) had an allograft in CR1 (175 high-risk [96 in ICE arm and 79 in HDS arm] and 18 standard-risk [6 in ICE arm and 12 in HDS arm]). Median and 5-year overall survival (OS) were 2.14 years and 38% in ICE arm compared to 4.51 years and 48% in SHD arm (P .0125), improving sensibly in the standard-risk subset (5-year OS 55% vs 72%, P .0068) and patients aged ≤60 years with de novo AML (5-year OS 43% vs 58%; P .0026). Median and 5-year DFS were 1.48 years and 36% compared to 3.41 years and 48% (P .0030), again improving in the standard-risk subset (5-year DFS 40% vs 64%; P .0064) and patients aged ≤60 years with de novo AML (5-year DFS 38% vs 54%; P .0023).
Conclusion
The current SHD schedule, albeit proving more toxic than standard ICE did not increase the risk of induction death and improved the CR rate and 5-year OS and DFS results, particularly in patients with standard-risk AML and aged ≤60 years with de novo AML.
Session topic: Standard Treatment Results in AML
Keyword(s): Acute myeloid leukemia, Adult, High dose therapy, Randomized
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Hall A2
Background
AML is curable in the fraction of patients who achieve complete remission (CR) and do not relapse following consolidation or allogeneic stem cell transplantation (ASCT). Therefore new strategies are continuously developed to overcome the risk of primary resistant or recurrent disease.
Aims
In NILG trial 02/06 [ClinicalTrials.gov Identifier: NCT00495287]a sequential high-dose (SHD) regimen was compared to standard induction, having CR rate as primary study objective. CR patients were eligible to risk-specific treatment.
Methods
Study patients were stratified by age 60 years and randomized to ICE (idarubicin 12 mg/m2/d iv. dd1-3, cytarabine 100 mg/m2/bd iv. dd 1-7, etoposide 100 mg/m2/d iv. dd1-5) or SHD (cytarabine 2 g [1 g if age >65]/m2/bd iv. dd 1-2 and 8-9, idarubicin 18 mg/m2/d iv. dd 3 and 10), plus G-CSF from d11. Postremission consolidation consisted of IC (cycle 2), intermediate-dose cytarabine 1 g/m2/bd iv. dd 1-4, with harvest of CD34+ blood stem cells (cycle 3), and allogeneic SCT if high-risk or second randomization to BUCY2-conditioned autograft or repetitive HD cycles (cytarabine 2 g/m2/bd iv. dd 1-5 and idarubicin 8 mg/m2/d dd 1-2, cycles 4-6) supported by 1-2 x106/kg CD34+ cells. The high-risk class was defined by cytogenetics, selected risk factors in intermediate/normal cytogenetic risk group (FLT3 ITD+, WBC >50, minimally differentiated/megakaryo-/erythro-blastic,secondary or MDS-related AML), and late CR. Results were analyzed by treatment intention and, to detect late survival differences, compared using the Kaplan-Meier estimate with weighted log-rank tests according to Fleming and Harrington.
Results
Between 2006-2012, 572 patients were enrolled (median age 52 years, range 16-73; 74% high-risk; 286 with comparable characteristics in each arm). After induction course, CR rate was 69.2% in ICE arm and 81.5% in SHD arm (P .001), due to lower resistance rate (25.2% vs 11.2%, P <.0001) without increased mortality (5.6% vs 7.3%, P .39). The benefit was confirmed in high-risk AML (n=201 vs 218: CR 64.2% vs 77.6%; P .002) and in patients aged ≤60 years with de novo AML (n=190 vs 189: CR 74.2% vs 86.2%; P .003). Overall CR rate after cycle 2/other salvage was 82.5% vs 86.0% (P .25). SHD increased the time to neutrophil/platelet recovery (P <.0001), the risk of infections (bacterial, P .0001; fungal, P .003) and hepatic, metabolic and cutaneous toxicity (P <.05), and was associated with longer intercycle intervals (P<.0001), lower feasibility of cycle 3 (P <.0001) and poorer stem cell mobilization (n=123 vs 93). One-hundred ninety-three patients (41%) had an allograft in CR1 (175 high-risk [96 in ICE arm and 79 in HDS arm] and 18 standard-risk [6 in ICE arm and 12 in HDS arm]). Median and 5-year overall survival (OS) were 2.14 years and 38% in ICE arm compared to 4.51 years and 48% in SHD arm (P .0125), improving sensibly in the standard-risk subset (5-year OS 55% vs 72%, P .0068) and patients aged ≤60 years with de novo AML (5-year OS 43% vs 58%; P .0026). Median and 5-year DFS were 1.48 years and 36% compared to 3.41 years and 48% (P .0030), again improving in the standard-risk subset (5-year DFS 40% vs 64%; P .0064) and patients aged ≤60 years with de novo AML (5-year DFS 38% vs 54%; P .0023).
Conclusion
The current SHD schedule, albeit proving more toxic than standard ICE did not increase the risk of induction death and improved the CR rate and 5-year OS and DFS results, particularly in patients with standard-risk AML and aged ≤60 years with de novo AML.
Session topic: Standard Treatment Results in AML
Keyword(s): Acute myeloid leukemia, Adult, High dose therapy, Randomized
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