Geoffrey L. Uy, MD, Professor of Medicine, Oncology Division, Washington University School of Medicine in St Louis, Missouri, reviews the safety and efficacy results from a phase 1b study on lower-dose CPX-351 plus venetoclax as a first-line treatment for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. These data were presented at ASH 2021.

Transcript:

My name's Geoff Uy. I am a Professor of Medicine in the Division of Oncology at Washington University School of Medicine.

Oncology Learning Network: What existing data led you and your co-investigators to conduct this research?

Dr Uy: This study looks at CPX351 or vyxeos, which is an FDA approved medication for older adults with high risk or secondary AML.

We know that this drug is superior to standard 7+3 for patients who are candidates for intensive chemotherapy. However, there are a number of patients, particularly older adults, who are not considered fit or appropriate for therapy.

The new standard of care with the VIALE-A data is a combination of a hypomethylating agent of venetoclax. We know that venetoclax can synergize with a number of different chemotherapeutic compounds, including low-dose (cytarabine) Ara-C, hypomethylating agents. There is merging data to suggest that it's also synergistic with conventional chemotherapy regimens, such as 7:3 or (fludarabine, cytarabine and filgrastim) FLAG-based regimens.

This was a way to test the ability of a chemotherapy regimen that we know is potentially more effective than standard 7+3. And then see if venetoclax can synergize with it.

OLN: Could you briefly describe the study and its findings?

Dr Uy: This was a phase 1B study where we conducted a dose escalation of CPX351 in conjunction with venetoclax. There were a couple different dose levels that were explored starting from 20 units of CPX351 plus venetoclax up to 40 units.

The CPX351 was given on a day 1 and 3 schedule. Venetoclax was given at 400 mg for 21 days.

In this study it was found that the 30 units dose given on days 1 and 3 was the recommended phase 2 dose. This followed into a dose expansion cohort in this patient population.

OLN: Were any of the outcomes particularly surprising?

Dr Uy: What we demonstrated is that we can give CPX351 with venetoclax safely.

The remission rates were 67% or two thirds of patients achieved a complete remission (CR), which is very much in line with the VIALE-A data, which also tested low intensity therapies in patients unsuitable for intensive induction. The MRD rates were also quite high. I believe they were in the high 50% range, which is also very similar to VIALE-A. The dose before the CPX351 was the 30 units on the day 1-3 schedule, which is only about a fifth of what we would conventionally give for patients receiving intensive chemotherapy.

This may be an efficacious regimen for this patient population, while exposing them to much lower doses of anthracyclines and chemotherapy compared to standard regimens.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Uy: This is an interesting study. The numbers are still relatively low. Only 17 patients were treated at the phase 2 dose, which was reported in this abstract. I think that we need additional data and more patients to really understand where this fits into the treatment paradigm.

OLN: Do you and your co-investigators intend to expand upon this research? If so, what will be your next steps?

Dr Uy: That's still a matter of debate and discussion--whether we move on to a much larger single arm study versus starting to do comparison studies with what we would consider standard of care.