Contributions
Abstract: EP456
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Azacitidine is a hypomethylating agent was until recently offered as monotherapy for older and frail patients as first line treatment. In relapsed or refractory (R/R) acute myeloid leukemia (AML), no randomized trial was conducted to position azacitidine (AZA) respective to other standards of care.
Aims
To compare the outcome of R/R AML treated with AZA, intensive chemotherapy (IC) or best supportive care (BSC).
Methods
Our work studied 526 AML refractory (Ref, N=171, 32.5%) to one course of intensive chemotherapy or relapsed after first complete remission (Rel, N=355, 67.5%) in Toulouse or Bordeaux university hospitals (DATAML registry) between 2007 and 2016. At R/R, they received either intensive chemotherapy (IC, N=270; Ref=112, Rel=158), azacitidine (AZA, N=97; Ref=13, Rel=84) or best supportive care (BSC, N=159; Ref=46; Rel=113).
Results
Median age was 64.3 years (IC: 60.1; AZA: 66.3; BSC: 69.4); ECOG performance status (PS) was 0-1 in 77.7% (IC: 82.7%; AZA: 86.6%; BSC: 64.4%). CCI comorbidities score was ≥1 in 34.7%, without difference between groups. Median WBC was 3.0.109/L (IQR, 1.54-7.2). Bone marrow blasts (BMB) at R/R were ≥20% in 63.9% (IC: 72%; AZA: 51.6%; BSC: 61.5%). Karyotypes were intermediate or adverse in 71.7% and 28.3% respectively. Myelodysplasia-related changes (MRC) were observed in 34.8%. At relapse, FLT3-ITD mutations were identified in 19/87 (22.4%; IC: 36.2%, AZA: 4.2%; BSC: 7.1%) and NPM1 mutations in 27/67 (40.3%; IC: 53.3%, AZA: 6.2%; BSC: 33.3%). IC regimens were mainly high-dose cytarabine associated to an anthracycline (N=105, 48.2%). In total, 148 patients received an anthracycline (54.8%) and median total cytarabine dose was 10 grams/m² (IQR, 5-24). 39.3% underwent alloSCT. Median number of AZA cycles was 4 (IQR: 2-8, range: 1-27). 10.3% underwent alloSCT. Complete response (CR or CRi) was 32.2% (IC: 37.0%, AZA: 18.6%; P=0.0008), and early death at day 30 rate was 11.6% (IC: 4.8%, AZA: 3.1%; BSC: 28.3%; P<0.0001). With AZA, CR (7.2%) or CRi (11.3%) occurred in median after 4.6 months (IQR, 2.8-7.3). Partial response (PR) was obtained in 2.1%, stable disease (SD) in 20.6%, hematological improvement (HI) in 15.5%. AZA was independently associated to a significantly lower rate of CR/CRi (OR, 0.23; P<0.0001).With a median follow-up of 56.1 months, the overall survival (OS) was 6.2 months (IC: 8.2 months [5-year: 15.6%]; AZA: 9.6 months [5-year: 6.0%]; BSC: 2.2 months [5-year: 1.7%]). With AZA, OS varied depending on response (CR/CRi: 27.2 months; PR/HI/SD: 12.5 months; failure: 5.3 months (P<0.0001). Independent predictive factors for OS were: for IC, age (HR, 1.53; P=0.002), ECOG PS (HR, 1.53; P=0.02), WBC (HR, 1.78; P=0.02), MRC-AML (HR, 1.57; P=0.002); for AZA, AML status (post-MDS/CMML: HR, 2.70; P=0.023; t-AML: HR, 0.26; P=0.001), BMB ≥20% (HR, 1.85; P=0.011), adverse cytogenetics (HR, 2.22; P=0.006), alloSCT at R/R (HR, 0.30; P=0.012). We then analyzed the effect of treatment using a Royston and Parmar model: after adjustment on confounding factors, death risk is significantly inferior in the AZA group during the first month, is not statistically different between 1 and 7 months, and becomes significantly superior from 8 months.
Conclusion
At R/R, AZA gives response and overall survival rate similar to those obtained at first line and could represent a fair therapeutical option for the most frail and older patients, but with few late survivors. Nevertheless, these results will need to be updated in a few years, when the treatment of 2nd line will involve associations between azacitidine and targeted therapies or immunotherapies.
Keyword(s): Acute myeloid leukemia, Azacitidine, Refractory, Relapse
Abstract: EP456
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Azacitidine is a hypomethylating agent was until recently offered as monotherapy for older and frail patients as first line treatment. In relapsed or refractory (R/R) acute myeloid leukemia (AML), no randomized trial was conducted to position azacitidine (AZA) respective to other standards of care.
Aims
To compare the outcome of R/R AML treated with AZA, intensive chemotherapy (IC) or best supportive care (BSC).
Methods
Our work studied 526 AML refractory (Ref, N=171, 32.5%) to one course of intensive chemotherapy or relapsed after first complete remission (Rel, N=355, 67.5%) in Toulouse or Bordeaux university hospitals (DATAML registry) between 2007 and 2016. At R/R, they received either intensive chemotherapy (IC, N=270; Ref=112, Rel=158), azacitidine (AZA, N=97; Ref=13, Rel=84) or best supportive care (BSC, N=159; Ref=46; Rel=113).
Results
Median age was 64.3 years (IC: 60.1; AZA: 66.3; BSC: 69.4); ECOG performance status (PS) was 0-1 in 77.7% (IC: 82.7%; AZA: 86.6%; BSC: 64.4%). CCI comorbidities score was ≥1 in 34.7%, without difference between groups. Median WBC was 3.0.109/L (IQR, 1.54-7.2). Bone marrow blasts (BMB) at R/R were ≥20% in 63.9% (IC: 72%; AZA: 51.6%; BSC: 61.5%). Karyotypes were intermediate or adverse in 71.7% and 28.3% respectively. Myelodysplasia-related changes (MRC) were observed in 34.8%. At relapse, FLT3-ITD mutations were identified in 19/87 (22.4%; IC: 36.2%, AZA: 4.2%; BSC: 7.1%) and NPM1 mutations in 27/67 (40.3%; IC: 53.3%, AZA: 6.2%; BSC: 33.3%). IC regimens were mainly high-dose cytarabine associated to an anthracycline (N=105, 48.2%). In total, 148 patients received an anthracycline (54.8%) and median total cytarabine dose was 10 grams/m² (IQR, 5-24). 39.3% underwent alloSCT. Median number of AZA cycles was 4 (IQR: 2-8, range: 1-27). 10.3% underwent alloSCT. Complete response (CR or CRi) was 32.2% (IC: 37.0%, AZA: 18.6%; P=0.0008), and early death at day 30 rate was 11.6% (IC: 4.8%, AZA: 3.1%; BSC: 28.3%; P<0.0001). With AZA, CR (7.2%) or CRi (11.3%) occurred in median after 4.6 months (IQR, 2.8-7.3). Partial response (PR) was obtained in 2.1%, stable disease (SD) in 20.6%, hematological improvement (HI) in 15.5%. AZA was independently associated to a significantly lower rate of CR/CRi (OR, 0.23; P<0.0001).With a median follow-up of 56.1 months, the overall survival (OS) was 6.2 months (IC: 8.2 months [5-year: 15.6%]; AZA: 9.6 months [5-year: 6.0%]; BSC: 2.2 months [5-year: 1.7%]). With AZA, OS varied depending on response (CR/CRi: 27.2 months; PR/HI/SD: 12.5 months; failure: 5.3 months (P<0.0001). Independent predictive factors for OS were: for IC, age (HR, 1.53; P=0.002), ECOG PS (HR, 1.53; P=0.02), WBC (HR, 1.78; P=0.02), MRC-AML (HR, 1.57; P=0.002); for AZA, AML status (post-MDS/CMML: HR, 2.70; P=0.023; t-AML: HR, 0.26; P=0.001), BMB ≥20% (HR, 1.85; P=0.011), adverse cytogenetics (HR, 2.22; P=0.006), alloSCT at R/R (HR, 0.30; P=0.012). We then analyzed the effect of treatment using a Royston and Parmar model: after adjustment on confounding factors, death risk is significantly inferior in the AZA group during the first month, is not statistically different between 1 and 7 months, and becomes significantly superior from 8 months.
Conclusion
At R/R, AZA gives response and overall survival rate similar to those obtained at first line and could represent a fair therapeutical option for the most frail and older patients, but with few late survivors. Nevertheless, these results will need to be updated in a few years, when the treatment of 2nd line will involve associations between azacitidine and targeted therapies or immunotherapies.
Keyword(s): Acute myeloid leukemia, Azacitidine, Refractory, Relapse