LATE RESPONSES AND OVERALL SURVIVAL (OS) FROM LONG TERM FOLLOW UP OF A RANDOMIZED PHASE 2 STUDY OF SGI-110 (GUADECITABINE) 5-DAY REGIMEN IN ELDERLY AML WHO ARE NOT ELIGIBLE FOR INTENSIVE CHEMOTHERAPY
EHA Library. Kropf P. 06/13/15; 100712; P571
Dr. Patricia Kropf
Contributions
Contributions
Abstract
Abstract: P571
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
SGI-110 (guadecitabine) is a novel hypomethylating agent (HMA) given subcutaneously (SC) and provides a prolonged in vivo exposure to its active moiety decitabine. We previously reported results from a multicenter randomized dose-response study of guadecitabine given at 2 doses in a 5-day regimen in 51 treatment naïve elderly AML patients not eligible for intensive chemotherapy (Yee et al, 2014). There was no significant differences in overall composite complete response (CRc: CR+CRp+CRi) or safety between the two doses; however 14 patients were still on treatment at the time of the analysis.
Aims
To report on long term follow up including additional late responders and overall survival (OS)
Methods
Previously untreated elderly (≥ 65y) AML patients who were not eligible to receive intensive chemotherapy were randomized 1:1 to either 60 or 90 mg/m2/d SC for 5-days in 28-day cycles. Overall composite CR (CRc: CR+CRp+CRi) was the primary endpoint. OS, and Safety were secondary endpoints.
Results
Fifty one patients were treated (24 and 27 on 60 and 90 mg/m2 doses respectively). Patients’ characteristics were generally balanced between the 2 doses and represented a poor prognosis population: 73% were ≥75 y old; 47% had poor risk cytogenetics; 45% secondary AML; and 35% poor performance status (PS 2). No differences in either CRc or CR were observed in the previous and current analysis between the 2 treatment doses so data are presented here for the overall patients treated. Two additional patients developed CR with longer follow up (one on each arm) bringing total patients with CR to 19 (37%) and the total patients with CRc to 29 (57%): 19 CR; 7 CRi, and 3 CRp. Median follow up now reached 21.1 months (m) (range 17.2-30.0 m). Median number of cycles administered was 5 (range 1-24). Of the 29 CRc patients, the majority (20 or 69% of responders) occurred after at least 3 cycles and 6 of them (21% of responders) occurred after at least 6 cycles. Two late responders occurred after 8 and 9 cycles respectively. With death events reported in 34/51 patients (67%) the median OS is 10.5 m (95% CI: 5.3-18.1 m). The most common Grade≥3 Adverse Events (AEs) assessed as drug-related by investigators were neutropenia and thrombocytopenia (35% each), febrile neutropenia (20%), leukopenia (18%), and anemia (16%).
Summary
Unlike cytotoxic chemotherapy where responses tend to occur in the first 2 cycles, AML responses with HMA guadecitabine tend to occur after multiple cycles with potential for late responses even after 6 cycles. Clinical activity as demonstrated by 57% CRc including 37% CR and median OS of 10.5 months in this elderly poor prognosis population is promising. A Phase 3 trial in previously untreated AML patients not eligible for intensive chemotherapy has been initiated with 5-day regimen at 60 mg/m2/d SC.
Keyword(s): AML, DNA methylation, Hypomethylation
Session topic: Acute myeloid leukemia - Clinical 4
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
SGI-110 (guadecitabine) is a novel hypomethylating agent (HMA) given subcutaneously (SC) and provides a prolonged in vivo exposure to its active moiety decitabine. We previously reported results from a multicenter randomized dose-response study of guadecitabine given at 2 doses in a 5-day regimen in 51 treatment naïve elderly AML patients not eligible for intensive chemotherapy (Yee et al, 2014). There was no significant differences in overall composite complete response (CRc: CR+CRp+CRi) or safety between the two doses; however 14 patients were still on treatment at the time of the analysis.
Aims
To report on long term follow up including additional late responders and overall survival (OS)
Methods
Previously untreated elderly (≥ 65y) AML patients who were not eligible to receive intensive chemotherapy were randomized 1:1 to either 60 or 90 mg/m2/d SC for 5-days in 28-day cycles. Overall composite CR (CRc: CR+CRp+CRi) was the primary endpoint. OS, and Safety were secondary endpoints.
Results
Fifty one patients were treated (24 and 27 on 60 and 90 mg/m2 doses respectively). Patients’ characteristics were generally balanced between the 2 doses and represented a poor prognosis population: 73% were ≥75 y old; 47% had poor risk cytogenetics; 45% secondary AML; and 35% poor performance status (PS 2). No differences in either CRc or CR were observed in the previous and current analysis between the 2 treatment doses so data are presented here for the overall patients treated. Two additional patients developed CR with longer follow up (one on each arm) bringing total patients with CR to 19 (37%) and the total patients with CRc to 29 (57%): 19 CR; 7 CRi, and 3 CRp. Median follow up now reached 21.1 months (m) (range 17.2-30.0 m). Median number of cycles administered was 5 (range 1-24). Of the 29 CRc patients, the majority (20 or 69% of responders) occurred after at least 3 cycles and 6 of them (21% of responders) occurred after at least 6 cycles. Two late responders occurred after 8 and 9 cycles respectively. With death events reported in 34/51 patients (67%) the median OS is 10.5 m (95% CI: 5.3-18.1 m). The most common Grade≥3 Adverse Events (AEs) assessed as drug-related by investigators were neutropenia and thrombocytopenia (35% each), febrile neutropenia (20%), leukopenia (18%), and anemia (16%).
Summary
Unlike cytotoxic chemotherapy where responses tend to occur in the first 2 cycles, AML responses with HMA guadecitabine tend to occur after multiple cycles with potential for late responses even after 6 cycles. Clinical activity as demonstrated by 57% CRc including 37% CR and median OS of 10.5 months in this elderly poor prognosis population is promising. A Phase 3 trial in previously untreated AML patients not eligible for intensive chemotherapy has been initiated with 5-day regimen at 60 mg/m2/d SC.
Reference: Yee K, Daver N, Kropf P, et al: European Hematology Association Meeting, June 12-15, 2104; Milan, Italy. Abstract S647
Keyword(s): AML, DNA methylation, Hypomethylation
Session topic: Acute myeloid leukemia - Clinical 4
Abstract: P571
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
SGI-110 (guadecitabine) is a novel hypomethylating agent (HMA) given subcutaneously (SC) and provides a prolonged in vivo exposure to its active moiety decitabine. We previously reported results from a multicenter randomized dose-response study of guadecitabine given at 2 doses in a 5-day regimen in 51 treatment naïve elderly AML patients not eligible for intensive chemotherapy (Yee et al, 2014). There was no significant differences in overall composite complete response (CRc: CR+CRp+CRi) or safety between the two doses; however 14 patients were still on treatment at the time of the analysis.
Aims
To report on long term follow up including additional late responders and overall survival (OS)
Methods
Previously untreated elderly (≥ 65y) AML patients who were not eligible to receive intensive chemotherapy were randomized 1:1 to either 60 or 90 mg/m2/d SC for 5-days in 28-day cycles. Overall composite CR (CRc: CR+CRp+CRi) was the primary endpoint. OS, and Safety were secondary endpoints.
Results
Fifty one patients were treated (24 and 27 on 60 and 90 mg/m2 doses respectively). Patients’ characteristics were generally balanced between the 2 doses and represented a poor prognosis population: 73% were ≥75 y old; 47% had poor risk cytogenetics; 45% secondary AML; and 35% poor performance status (PS 2). No differences in either CRc or CR were observed in the previous and current analysis between the 2 treatment doses so data are presented here for the overall patients treated. Two additional patients developed CR with longer follow up (one on each arm) bringing total patients with CR to 19 (37%) and the total patients with CRc to 29 (57%): 19 CR; 7 CRi, and 3 CRp. Median follow up now reached 21.1 months (m) (range 17.2-30.0 m). Median number of cycles administered was 5 (range 1-24). Of the 29 CRc patients, the majority (20 or 69% of responders) occurred after at least 3 cycles and 6 of them (21% of responders) occurred after at least 6 cycles. Two late responders occurred after 8 and 9 cycles respectively. With death events reported in 34/51 patients (67%) the median OS is 10.5 m (95% CI: 5.3-18.1 m). The most common Grade≥3 Adverse Events (AEs) assessed as drug-related by investigators were neutropenia and thrombocytopenia (35% each), febrile neutropenia (20%), leukopenia (18%), and anemia (16%).
Summary
Unlike cytotoxic chemotherapy where responses tend to occur in the first 2 cycles, AML responses with HMA guadecitabine tend to occur after multiple cycles with potential for late responses even after 6 cycles. Clinical activity as demonstrated by 57% CRc including 37% CR and median OS of 10.5 months in this elderly poor prognosis population is promising. A Phase 3 trial in previously untreated AML patients not eligible for intensive chemotherapy has been initiated with 5-day regimen at 60 mg/m2/d SC.
Keyword(s): AML, DNA methylation, Hypomethylation
Session topic: Acute myeloid leukemia - Clinical 4
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
SGI-110 (guadecitabine) is a novel hypomethylating agent (HMA) given subcutaneously (SC) and provides a prolonged in vivo exposure to its active moiety decitabine. We previously reported results from a multicenter randomized dose-response study of guadecitabine given at 2 doses in a 5-day regimen in 51 treatment naïve elderly AML patients not eligible for intensive chemotherapy (Yee et al, 2014). There was no significant differences in overall composite complete response (CRc: CR+CRp+CRi) or safety between the two doses; however 14 patients were still on treatment at the time of the analysis.
Aims
To report on long term follow up including additional late responders and overall survival (OS)
Methods
Previously untreated elderly (≥ 65y) AML patients who were not eligible to receive intensive chemotherapy were randomized 1:1 to either 60 or 90 mg/m2/d SC for 5-days in 28-day cycles. Overall composite CR (CRc: CR+CRp+CRi) was the primary endpoint. OS, and Safety were secondary endpoints.
Results
Fifty one patients were treated (24 and 27 on 60 and 90 mg/m2 doses respectively). Patients’ characteristics were generally balanced between the 2 doses and represented a poor prognosis population: 73% were ≥75 y old; 47% had poor risk cytogenetics; 45% secondary AML; and 35% poor performance status (PS 2). No differences in either CRc or CR were observed in the previous and current analysis between the 2 treatment doses so data are presented here for the overall patients treated. Two additional patients developed CR with longer follow up (one on each arm) bringing total patients with CR to 19 (37%) and the total patients with CRc to 29 (57%): 19 CR; 7 CRi, and 3 CRp. Median follow up now reached 21.1 months (m) (range 17.2-30.0 m). Median number of cycles administered was 5 (range 1-24). Of the 29 CRc patients, the majority (20 or 69% of responders) occurred after at least 3 cycles and 6 of them (21% of responders) occurred after at least 6 cycles. Two late responders occurred after 8 and 9 cycles respectively. With death events reported in 34/51 patients (67%) the median OS is 10.5 m (95% CI: 5.3-18.1 m). The most common Grade≥3 Adverse Events (AEs) assessed as drug-related by investigators were neutropenia and thrombocytopenia (35% each), febrile neutropenia (20%), leukopenia (18%), and anemia (16%).
Summary
Unlike cytotoxic chemotherapy where responses tend to occur in the first 2 cycles, AML responses with HMA guadecitabine tend to occur after multiple cycles with potential for late responses even after 6 cycles. Clinical activity as demonstrated by 57% CRc including 37% CR and median OS of 10.5 months in this elderly poor prognosis population is promising. A Phase 3 trial in previously untreated AML patients not eligible for intensive chemotherapy has been initiated with 5-day regimen at 60 mg/m2/d SC.
Reference: Yee K, Daver N, Kropf P, et al: European Hematology Association Meeting, June 12-15, 2104; Milan, Italy. Abstract S647
Keyword(s): AML, DNA methylation, Hypomethylation
Session topic: Acute myeloid leukemia - Clinical 4
{{ help_message }}