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.
Keywords: IDH1; acute myeloid leukemia; hypomethylating agents; immunotherapy; ivosidenib; low-dose cytarabine; non-intensive chemotherapy; systematic literature review; targeted therapy; venetoclax.
Acute myeloid leukemia (AML) is a type of cancer of the bone marrow and blood that leads to overproduction of immature white blood cells. High-dose (intensive) chemotherapy is usually the first treatment option for AML. However, more than half of people newly diagnosed with AML cannot receive the recommended initial intensive chemotherapy due to older age or poor health. Treatment with low-dose cytarabine (LDAC) and hypomethylating agents (HMAs), such as azacitidine, is key for such people. We reviewed 26 clinical trials looking into available and developing treatment options for people who cannot have the recommended initial chemotherapy. The review found evidence that combining LDAC or HMA with a targeted therapy can improve survival. In AML, new therapies (such as ivosidenib, venetoclax and glasdegib) ‘target’ specific changes in the genes of cancer cells to slow or stop their division and growth. The greatest improvement in survival was seen in clinical trials where targeted therapies were added to azacitidine or LDAC. Targeted therapies may result in certain side effects that require regular monitoring. To provide patients with the benefits of targeted therapies they need to undergo genetic testing at the time of diagnosis. Tests to determine an individual's specific gene changes allows clinicians to develop personalised treatment plans with available targeted therapies. This shows promise in improving survival for people with AML who cannot receive initial intensive chemotherapy.