Contributions
Abstract: PB1395
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Intensive induction therapy in patients (pts) with acute myeloid leukemia (AML) can induce complete remission (CR) and is often followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplant (HSCT) in eligible patients. However, in elderly pts with AML who are HSCT-ineligible, relapse rates are relatively high, overall survival (OS) rates are low, and pts have limited treatment options. Maintenance/post-remission therapy intends to prolong the duration of remission and survival in pts with AML; however, additional studies are required to evaluate maintenance options for HSCT-ineligible pts.
Aims
Identify clinical studies from a systematic literature review (SLR) of randomized controlled trials (RCTs) to assess the efficacy and safety of maintenance therapy in HSCT-ineligible adult pts ≥18 y with newly diagnosed AML who have achieved CR or CR with incomplete platelet recovery (CRi) after intensive chemotherapy induction, with or without consolidation.
Methods
An SLR of RCTs reporting efficacy (OS, relapse/disease/event-free survival [RFS/DFS/EFS], and time to relapse), time to discontinuation, and safety of maintenance therapy was performed to identify relevant studies from 2005–2020 indexed in MEDLINE®, Embase, and EBM Reviews databases (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment Database) using controlled vocabulary and keywords. A supplementary search of clinicaltrials.gov, the FDA database, and abstracts from selected hematology conferences (2018–2019) was also conducted. Two independent reviewers determined eligibility and quality of all studies for inclusion using the Population, Intervention, Comparator, Outcomes, Study Design, and Time framework.
Results
The SLR identified 6701 citations through database searches and 1 from a supplementary search; of these, 25 publications were included in the review representing 22 distinct RCTs. All 22 studies included a maintenance phase with treatments across 3 broad classes of drugs (hypomethylating agents [n=8], immunotherapies [n=7], and anthracyclines [n=4]) and 3 other therapies, although variability in study design was significant. Of the 16 trials with pts randomized to maintenance therapy, 13 trials were designed to assess the efficacy of different maintenance therapies with the baseline population comprising pts randomized to maintenance therapy and outcomes reported by maintenance arm. The remaining trials were designed to assess the efficacy of induction (n=7) and consolidation therapies (n=2). All 13 trials with the primary analysis of maintenance therapy reported RFS/DFS/EFS by maintenance treatment arm, and 11 studies reported OS. Although time zero definitions for RFS/DFS/EFS and OS differed across trials, median RFS/DFS/EFS and median OS ranged from 5–16 and 10–39 mo, respectively. Only the QUAZAR trial of oral azacitidine demonstrated significant improvements in both RFS and OS with maintenance therapy (Table). A total of 17 studies reported safety outcomes related to maintenance therapy, with infection being the most commonly reported adverse event (n=10).
Conclusion
This SLR identified 22 RCTs reporting efficacy and safety data on maintenance therapies in the treatment of AML in adult pts who achieved CR/CRi and were ineligible for HSCT. Study design varied significantly. Few RCTs eligible for review were adequately designed to assess the efficacy of maintenance therapies and only 1 study demonstrated a significant survival benefit with maintenance therapy.
Keyword(s): Acute myeloid leukemia, Azacitidine, Clinical data, Systematic review
Abstract: PB1395
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Intensive induction therapy in patients (pts) with acute myeloid leukemia (AML) can induce complete remission (CR) and is often followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplant (HSCT) in eligible patients. However, in elderly pts with AML who are HSCT-ineligible, relapse rates are relatively high, overall survival (OS) rates are low, and pts have limited treatment options. Maintenance/post-remission therapy intends to prolong the duration of remission and survival in pts with AML; however, additional studies are required to evaluate maintenance options for HSCT-ineligible pts.
Aims
Identify clinical studies from a systematic literature review (SLR) of randomized controlled trials (RCTs) to assess the efficacy and safety of maintenance therapy in HSCT-ineligible adult pts ≥18 y with newly diagnosed AML who have achieved CR or CR with incomplete platelet recovery (CRi) after intensive chemotherapy induction, with or without consolidation.
Methods
An SLR of RCTs reporting efficacy (OS, relapse/disease/event-free survival [RFS/DFS/EFS], and time to relapse), time to discontinuation, and safety of maintenance therapy was performed to identify relevant studies from 2005–2020 indexed in MEDLINE®, Embase, and EBM Reviews databases (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment Database) using controlled vocabulary and keywords. A supplementary search of clinicaltrials.gov, the FDA database, and abstracts from selected hematology conferences (2018–2019) was also conducted. Two independent reviewers determined eligibility and quality of all studies for inclusion using the Population, Intervention, Comparator, Outcomes, Study Design, and Time framework.
Results
The SLR identified 6701 citations through database searches and 1 from a supplementary search; of these, 25 publications were included in the review representing 22 distinct RCTs. All 22 studies included a maintenance phase with treatments across 3 broad classes of drugs (hypomethylating agents [n=8], immunotherapies [n=7], and anthracyclines [n=4]) and 3 other therapies, although variability in study design was significant. Of the 16 trials with pts randomized to maintenance therapy, 13 trials were designed to assess the efficacy of different maintenance therapies with the baseline population comprising pts randomized to maintenance therapy and outcomes reported by maintenance arm. The remaining trials were designed to assess the efficacy of induction (n=7) and consolidation therapies (n=2). All 13 trials with the primary analysis of maintenance therapy reported RFS/DFS/EFS by maintenance treatment arm, and 11 studies reported OS. Although time zero definitions for RFS/DFS/EFS and OS differed across trials, median RFS/DFS/EFS and median OS ranged from 5–16 and 10–39 mo, respectively. Only the QUAZAR trial of oral azacitidine demonstrated significant improvements in both RFS and OS with maintenance therapy (Table). A total of 17 studies reported safety outcomes related to maintenance therapy, with infection being the most commonly reported adverse event (n=10).
Conclusion
This SLR identified 22 RCTs reporting efficacy and safety data on maintenance therapies in the treatment of AML in adult pts who achieved CR/CRi and were ineligible for HSCT. Study design varied significantly. Few RCTs eligible for review were adequately designed to assess the efficacy of maintenance therapies and only 1 study demonstrated a significant survival benefit with maintenance therapy.
Keyword(s): Acute myeloid leukemia, Azacitidine, Clinical data, Systematic review