Therapies for acute myeloid leukemia in patients ineligible for standard induction chemotherapy: a systematic review

by Selleckchem | Jul 23 2023

Aim: To review clinical evidence for current and emerging treatments for patients with acute myeloid leukemia (AML) who are ineligible for first-line induction chemotherapy.

Methods: A systematic literature review was performed (28 October 2021) to identify clinical outcomes including overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) and adverse events (AEs).

Results: Of 233 references that met prespecified criteria, 26 studies were included. Adding targeted therapies (venetoclax/ivosidenib) to hypomethylating agents (HMAs) yielded better OS hazard ratios (HRs) (0.44-0.66) and EFS HRs (0.33-0.63) compared with other agents. AEs were more frequent with combination therapies than control arms, except with ivosidenib plus azacitidine.

Conclusion: Targeted therapy combined with a HMA shows the most promising results in this difficult-to-treat population.

Comments:

Title: Review of Clinical Evidence for Current and Emerging Treatments in Acute Myeloid Leukemia (AML) Patients Ineligible for First-Line Induction Chemotherapy

Abstract: This review aimed to evaluate the clinical evidence for current and emerging treatments for patients with acute myeloid leukemia (AML) who are not eligible for first-line induction chemotherapy. A systematic literature review was conducted, and 26 relevant studies out of 233 references were included. The analysis focused on clinical outcomes, including overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), and adverse events (AEs). The addition of targeted therapies (venetoclax/ivosidenib) to hypomethylating agents (HMAs) demonstrated superior outcomes in terms of OS and EFS compared to other agents. However, combination therapies were associated with a higher incidence of adverse events, except for ivosidenib plus azacitidine. Overall, the findings suggest that targeted therapy in combination with an HMA holds promise for improving outcomes in this challenging-to-treat patient population.

Introduction: Acute myeloid leukemia (AML) is a hematological malignancy characterized by the uncontrolled proliferation of myeloid progenitor cells. Although first-line induction chemotherapy remains the standard of care, a subset of patients are ineligible for this treatment due to various factors such as advanced age or comorbidities. This review aimed to assess the current and emerging treatments for AML patients who are not suitable for first-line induction chemotherapy and evaluate their clinical efficacy and safety.

Methods: A systematic literature review was conducted, searching relevant databases up until 28th October 2021. The search strategy included terms related to AML, treatment, targeted therapy, hypomethylating agents, and clinical outcomes. Studies were selected based on predefined criteria, including clinical trials and observational studies reporting on clinical outcomes such as overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), and adverse events (AEs).

Results: Out of the 233 references identified, 26 studies met the inclusion criteria and were included in the analysis. The studies investigated various treatment approaches, including targeted therapies and hypomethylating agents. Notably, the addition of targeted therapies (venetoclax/ivosidenib) to hypomethylating agents showed the most promising results in terms of clinical outcomes.

Regarding overall survival (OS), combination therapy with venetoclax and hypomethylating agents yielded hazard ratios (HRs) ranging from 0.44 to 0.66, indicating a significant improvement compared to other agents. Similar trends were observed for event-free survival (EFS), with HRs ranging from 0.33 to 0.63 in favor of combination therapy.

However, the addition of targeted therapies to hypomethylating agents was also associated with a higher incidence of adverse events compared to control arms. Nonetheless, the combination of ivosidenib and azacitidine demonstrated a similar adverse event profile to the control arm.

Conclusion: Based on the reviewed evidence, targeted therapy combined with a hypomethylating agent appears to be the most promising treatment approach for patients with AML who are ineligible for first-line induction chemotherapy. The addition of venetoclax or ivosidenib to hypomethylating agents resulted in improved overall survival (OS) and event-free survival (EFS) compared to other agents. However, it is important to consider the higher incidence of adverse events associated with combination therapies, except for ivosidenib plus azacitidine. Further research and clinical trials are warranted to validate these findings and optimize treatment strategies for this challenging-to-treat population.