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Abstract

Abstract: P208

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
Effects on overall survival (OS) are of primary importance when evaluating AML treatments (Tx). Though complete remission (CR) rates are lower with azacitidine (AZA) than with intensive chemotherapy (IC), OS is similar with AZA and IC (Dombret et al, Blood, 2015). The 2017 European LeukemiaNet (ELN) recommendations acknowledge that hypomethylating agents, including AZA, may alter the natural course of AML in some patients (pts) who do not achieve CR (Döhner et al, Blood, 2017). According to IWG criteria for AML (Cheson et al, J Clin Oncol, 2003), stable disease (SD) is considered non-response to Tx. Yet AML is a progressive disease; potentially, stable health status may reflect delayed disease progression and result in improved OS.

Aims
This post hoc analysis evaluated OS outcomes among older pts with AML treated with AZA or conventional care regimens (CCR) who maintained SD, with or without hematologic improvement (HI), in the phase 3 AZA-AML-001 study.

Methods
Pts aged ≥65 years with AML (>30% marrow blasts), ECOG PS score ≤2, NCCN-defined intermediate- or poor-risk cytogenetics, and WBC count ≤15x109/L received AZA (75mg/m2 x7 days [d]/28d cycle) or a CCR (IC [standard 7+3 regimen], low-dose cytarabine [20mg BID x 10d/28d cycle], or best supportive care). OS was assessed using Kaplan-Meier methods for pts with SD at 2-, 4-, and 6-month landmarks. SD was protocol-defined as the absence of an IWG-defined AML response and no progressive disease (PD), whether or not HI was attained. Pts with SD could have had an IWG-defined response or PD at any time other than at the specified landmarks. OS was also evaluated in pts with HI as their best response; attainment of HI must have begun on or before, and been sustained past, each landmark, and lasted for ≥56 consecutive days.

Results
Median OS for all SD pts was 2.1-2.5 months longer with AZA vs CCR, and estimated 1-year survival was ~15% higher at each landmark in the AZA arm (Table). Hazard ratios for OS among all SD pts treated with AZA vs CCR ranged from 0.81–0.88. Median OS among pts with SD and no HI ranged from 12.6–13.3 months in the AZA arm and from 11.1-12.2 months in the CCR arm. Within Tx arms, AZA-treated pts with HI had meaningfully improved OS at all landmarks, ranging from 3.7 to 7.9 months longer than OS for pts without HI (Table). In contrast, HI attained with CCR did not largely influence OS; differences between pts who attained HI vs no HI ranged from -0.2 to 2.9 months. Median durations of HI in the AZA vs CCR arms, respectively, were 183 vs 166 days at 2 months, 176 vs 148 days at 4 months, and 176 vs 138 days at 6 months. Estimated 1-year survival within the AZA arm was 4.9%–27.4% greater for pts with HI than for pts with no HI, but for CCR-treated pts with HI, 1-year survival was 0%–10.3% greater. Between Tx arms, 1-year survival with AZA in pts with HI was 9.6%–33.3% greater than for CCR-treated pts with HI.

Conclusion
Maintaining SD during AZA or CCR Tx is associated with relatively favorable OS outcomes, as median OS in pts with SD exceeded that for all pts in the AZA-AML-001 trial (10.4 months with AZA vs 6.5 months with CCR; Dombret et al, Blood, 2015). Pts with SD who also attained HI during early AZA Tx had meaningfully improved OS, whereas similar CCR-treated pts did not, suggesting that HI with AZA is qualitatively different from HI with CCR. The prognostic relevance of HI in AML requires further study.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Survival, Clinical outcome, Acute Myeloid Leukemia

Abstract: P208

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
Effects on overall survival (OS) are of primary importance when evaluating AML treatments (Tx). Though complete remission (CR) rates are lower with azacitidine (AZA) than with intensive chemotherapy (IC), OS is similar with AZA and IC (Dombret et al, Blood, 2015). The 2017 European LeukemiaNet (ELN) recommendations acknowledge that hypomethylating agents, including AZA, may alter the natural course of AML in some patients (pts) who do not achieve CR (Döhner et al, Blood, 2017). According to IWG criteria for AML (Cheson et al, J Clin Oncol, 2003), stable disease (SD) is considered non-response to Tx. Yet AML is a progressive disease; potentially, stable health status may reflect delayed disease progression and result in improved OS.

Aims
This post hoc analysis evaluated OS outcomes among older pts with AML treated with AZA or conventional care regimens (CCR) who maintained SD, with or without hematologic improvement (HI), in the phase 3 AZA-AML-001 study.

Methods
Pts aged ≥65 years with AML (>30% marrow blasts), ECOG PS score ≤2, NCCN-defined intermediate- or poor-risk cytogenetics, and WBC count ≤15x109/L received AZA (75mg/m2 x7 days [d]/28d cycle) or a CCR (IC [standard 7+3 regimen], low-dose cytarabine [20mg BID x 10d/28d cycle], or best supportive care). OS was assessed using Kaplan-Meier methods for pts with SD at 2-, 4-, and 6-month landmarks. SD was protocol-defined as the absence of an IWG-defined AML response and no progressive disease (PD), whether or not HI was attained. Pts with SD could have had an IWG-defined response or PD at any time other than at the specified landmarks. OS was also evaluated in pts with HI as their best response; attainment of HI must have begun on or before, and been sustained past, each landmark, and lasted for ≥56 consecutive days.

Results
Median OS for all SD pts was 2.1-2.5 months longer with AZA vs CCR, and estimated 1-year survival was ~15% higher at each landmark in the AZA arm (Table). Hazard ratios for OS among all SD pts treated with AZA vs CCR ranged from 0.81–0.88. Median OS among pts with SD and no HI ranged from 12.6–13.3 months in the AZA arm and from 11.1-12.2 months in the CCR arm. Within Tx arms, AZA-treated pts with HI had meaningfully improved OS at all landmarks, ranging from 3.7 to 7.9 months longer than OS for pts without HI (Table). In contrast, HI attained with CCR did not largely influence OS; differences between pts who attained HI vs no HI ranged from -0.2 to 2.9 months. Median durations of HI in the AZA vs CCR arms, respectively, were 183 vs 166 days at 2 months, 176 vs 148 days at 4 months, and 176 vs 138 days at 6 months. Estimated 1-year survival within the AZA arm was 4.9%–27.4% greater for pts with HI than for pts with no HI, but for CCR-treated pts with HI, 1-year survival was 0%–10.3% greater. Between Tx arms, 1-year survival with AZA in pts with HI was 9.6%–33.3% greater than for CCR-treated pts with HI.

Conclusion
Maintaining SD during AZA or CCR Tx is associated with relatively favorable OS outcomes, as median OS in pts with SD exceeded that for all pts in the AZA-AML-001 trial (10.4 months with AZA vs 6.5 months with CCR; Dombret et al, Blood, 2015). Pts with SD who also attained HI during early AZA Tx had meaningfully improved OS, whereas similar CCR-treated pts did not, suggesting that HI with AZA is qualitatively different from HI with CCR. The prognostic relevance of HI in AML requires further study.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Survival, Clinical outcome, Acute Myeloid Leukemia

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