​​Dr DiNardo on Alternative Triplet Regimens For Select Patients With AML

Courtney DiNardo, MD, MSCE, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses triplets that serve as alternatives to standard-of-care approaches with azacitidine (Vidarza) and venetoclax (Venclexta) doublet therapy in select patients with acute myeloid leukemia (AML).

There is significant unmet need for patients with FLT3-ITD mutated AML, DiNardo begins. This population is characterized as having aggressive disease and is at a higher risk of relapse. Additionally, these patients have historically poor prognosis, and achieve suboptimal responses with standard AML treatments, DiNardo says.

To address the need for more effective, targeted treatments in this space, the addition of an FLT3 inhibitor to azacitidine and venetoclax is being investigated, DiNardo details. Initial findings suggest improved responses with this combination therapy. Although there are concerns regarding the regimen’s tolerability in older, less fit patients with AML, she adds. Current data indicate that the regimen is safe in this population provided that dosing is modified to minimize adverse effects.

Additionally, DiNardo notes that patients who present with a monocytic phenotype, which is often accompanied by signaling mutations, may experience benefit with the inclusion of purine analogs like cladribine or fludarabine alongside the azacitidine and venetoclax backbone. These analogs may complement therapy and enhance outcomes in this specific subset of patients, she explains.

Although patients with IDH mutations generally experience responses with azacitidine and venetoclax, this combination is not curative, DiNardo continues. Accordingly, the use of IDH inhibitors in combination with this standard approach is being explored. The goal is to determine whether IDH 1/2 inhibitors can further optimize outcomes for these targeted subsets, DiNardo says.

Ultimately, the management of FLT3-ITD–mutated AML is evolving, with an emphasis on combining different therapeutic agents to improve response rates and overall outcomes. This approach, along with tailored dosing adjustments and the integration of additional agents, offers promise in addressing the specific needs of this patient population, DiNardo concludes.