Recently Introduced Low-Intensity Options for Older Patients With AML

Tapan Kadia, MD, professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, discusses the recent and upcoming changes in treatment of acute myeloid leukemia (AML) for patients who are not candidates for intensive remission induction therapy.

Kadia says the development of new drugs has made it possible to achieve high rates of complete remission and improved overall survival (OS) when treating older patients with AML. Venetoclax (Venclexta) combined with either of the hypomethylating agents azacitadine (Vidaza) or decitabine (Dacogen) have become preferred regimens for patients with no actionable mutations, while patients with IDH1 and IDH2 mutations can benefit from the targeted therapies ivosidenib (Tibsovo) and enasidenib (Idhifa).

According to Kadia, new trials are investigating combination therapies, such as the AGILE study (NCT03173248) of ivosidenib plus azacitadine in patients with IDH1-positive AML, which showed superior 1-year event-free survival and OS versus azacitadine and placebo, as well as favorable tolerability. Regimens like these offer significant benefit to patients with AML without intensive chemotherapy.

TRANSCRIPTION:

0:08 | In older patients, that’s where the biggest change has occurred with the development of drugs like venetoclax, as well as IDH1 and IDH2 inhibitors. The use of hypomethylating agents such as azacitadine and decitabine combined with venetoclax has allowed us to treat a higher proportion of older patients with semi-curative intent where we are achieving higher rates of complete remission with a combination and improving OS. The use of other targeted therapies is also important in this population. For example, [for] those who are unable to tolerate chemotherapy, there are now options in the frontline of using single-agent IDH1 and IDH2 inhibitors in patients who have those mutations.

0:57 | There are also now trials looking at combination strategies with IDH inhibitors with [azacitadine]. The most prominent being the recent AGILE study, which demonstrated the improvement in outcomes with the combination of azacitidine and ivosidenib in newly diagnosed patients with IDH1-mutated AML, which I think will become a standard of care in that subset in patients who are unable to tolerate intensive chemotherapy. [There are] a lot of options in older [patients with] AML and those patients who are unfit for intensive chemotherapy with low intensity therapy plus venetoclax and other targeted agents.