Chetasi Talati, MD, an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center, discusses the design of a chart review study with venetoclax (Venclexta) and hypomethylating agents (HMAs) in older patients with newly-diagnosed acute myeloid leukemia (AML).

2020 European Hematology Association Annual Congress

 included adult patients with AML who received venetoclax in combination with HMAs or low-dose cytarabine (Cytosar-U®). In this multicenter, retrospective study, Talati explains that investigators are trying to assess how venetoclax is being used in the real-world setting. There are differing opinions on how to best utilize HMA/venetoclax combinations in this space, says Talati. Different geographical areas and institutions all have their own standards of care. Additionally, the antimicrobial agents that are being used as prophylactic medications, dose reductions with venetoclax and HMAs, and scheduling of medications all varies depending on the practice, says Talati.

Additionally, in older patients specifically, there is a group of patients who are still considered borderline to receive intensive chemotherapy, adds Talati. It is unknown whether a HMA/venetoclax combination is more beneficial than intensive chemotherapy in this patient population. That type of prospective study may never be conducted; therefore the idea behind this research is to use retrospective data collected from multiple institutions on patients who have been treated with different approaches, dosing schema, and schedules, and compare them with intensive chemotherapy regimens, concludes Talati.

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Chetasi Talati, MD, discusses the design of a chart review study with venetoclax and hypomethylating agents in older patients with newly-diagnosed acute myeloid leukemia.

Dr. Talati on Rationale for Collecting Real-World Data on Venetoclax/HMA Combos in AML

Chetasi Talati, MD, hematologic oncology, Moffitt Cancer Center, assistant member, Moffitt Cancer Center in the Department of Malignant Hematology, discusses the rationale for investigating venetoclax (Venclexta) in acute myeloid leukemia (AML).

Venetoclax has had significant impact in hematologic malignancies such as chronic lymphocytic leukemia and multiple myeloma, says Talati.

AML is associated with a high level of BCL-2 expression, explains Talati. Therefore, venetoclax could potentially induce anti-leukemic effects in this patient population.

Initial data showed that, as monotherapy, venetoclax induced modest response rates in the relapsed/refractory setting. However, in November 2018, the FDA granted an accelerated approval to venetoclax in combination with the hypomethylating agent azacitidine or decitabine or low-dose cytarabine for the treatment of patients with newly diagnosed AML who are over the age of 75, or who are ineligible for intensive induction chemotherapy due to comorbidities. Data from the phase 3 VIALE-A trial showed that the combination of venetoclax and azacitidine led to a 34% reduction in the risk of death versus azacitidine alone in this patient population. The results from the trial, which were presented during the 2020 European Hematology Association Congress, are practice changing, concludes Talati.

Chetasi Talati, MD, discusses the rationale for investigating venetoclax in acute myeloid leukemia.



Dr. Talati on the Rationale for Venetoclax in AML

Chetasi Talati, MD, hematologic oncology, Moffitt Cancer Center, assistant member, Moffitt Cancer Center in the Department of Malignant Hematology, discusses the ongoing safety analysis of venetoclax (Venclexta)-based combinations in patients with newly diagnosed acute myeloid leukemia.

One factor in the AML Real World Evidence Initiative that is currently under scrupulous investigation is treatment-related mortality, says Talati. Final data have not yet been reported, however, when looking at premlinary results at  3 and 6 months, investigators saw Kaplan Meier survival rates of 100% versus 79% for venetoclax treatment combined with hypomethylating agents (HMAs) and 75% versus 48% in the control cohort, which was comprised of high-intensity treatments and other cytarabine-based regimens.

This preliminary data truly shed light on how well venetoclax plus HMAs is tolerated in this patient population; however, longer-term follow-up is needed, and investigators are particularly interested in seeing the 30-day and 60-day mortality rates with the venetoclax-based combinations, says Talati.

Additionally, investigators continue to study the adverse events associated with the agent, specifically cytopenia and invasive fungal infections. To this end, data regarding the number of hospitalizations that could potentially result in treatment interruptions continue to be collected, concludes Talati. 

 Chetasi Talati, MD, discusses the ongoing safety analysis of venetoclax (Venclexta)-based combinations in patients with newly diagnosed acute myeloid leukemia.

Chetasi Talati, MD

Articles

Dr. Talati on Rationale for Collecting Real-World Data on Venetoclax/HMA Combos in AML

Dr. Talati on the Rationale for Venetoclax in AML

Dr. Talati on Real-World Data With Venetoclax Combinations in AML