Evaluating Venetoclax as a Maintenance Therapy After Transplant for AML Patients

Acute myeloid leukemia (AML) remains challenging to treat. Even after a successful allogeneic stem cell transplant (allo-SCT), relapse can occur. Prolonging remission and improving quality of life after SCT is an important focus of AML research.  Researchers are currently studying venetoclax (Venclexta, AbbVie/Genentech) as maintenance therapy after transplant. Venetoclax is a medication that targets leukemia cells’ survival pathways.

Current FDA approval for venetoclax in AML

Venetoclax is currently FDA-approved in combination with azacitidine, decitabine, or low-dose cytarabine for adults with newly diagnosed AML who are age 75 or older or who cannot receive intensive chemotherapy. This approval is based on evidence that venetoclax in these combinations improves remission rates and overall survival for these patients.

Venetoclax as maintenance therapy after transplant

While allo-SCT can offer long-term remission, many patients relapse within the first year. Maintenance therapy is given after transplant to reduce the risk of relapse. Previous research tested azacitidine alone as maintenance therapy. This delayed relapse but did not clearly improve survival. Because venetoclax combined with azacitidine has shown higher remission rates in people with newly diagnosed AML, researchers are testing if this combination could extend remission after transplant. 

Recently, updates we shared  venetoclax in combination with intensive chemotherapy for newly diagnosed and relapsed/refractory AML patients, you can read it here: Trial Results of FLAG-IDA and Venetoclax for AML

Evidence from early studies

A phase 1 study at Dana-Farber Cancer Institute tested prophylactic venetoclax plus azacitidine (Ven/Aza) maintenance in patients with high-risk AML or myelodysplastic syndromes (MDS) after reduced-intensity conditioning transplants.

• Treatment approach: Azacitidine was given on days 1-5 and venetoclax on days 1-14 of each cycle.

• Safety findings: Side effects mainly included temporary low blood counts (neutropenia, thrombocytopenia), but infections were uncommon. Rates of graft-versus-host disease (GVHD) were not higher than expected.

• Outcomes: After two years, overall survival was 67% and progression-free survival was 59%. Some patients achieved measurable residual disease (MRD) clearance during maintenance, a sign of deeper remission.

These results showed the regimen could be administered safely and warranted further study in larger, randomized trials.

The VIALE-T phase 3 trial

The VIALE-T study is a global phase 3 trial designed to confirm whether venetoclax plus azacitidine can improve survival as maintenance after allo-SCT in AML. This study is currently active but not recruiting new participants. Its objective is to compare venetoclax with azacitidine against best supportive care. This study is divided into two parts: part 1 determined the appropriate dose; and part 2 randomized patients aged 12 years and older.

Evaluate overall survival and relapse-free survival after transplant.

Venetoclax may become a part of many therapeutic applications for AML 

Venetoclax is FDA-approved for older adults with newly diagnosed AML, but it remains under study for use after transplant maintenance. Early data suggest it can be delivered safely and may help reduce relapse risk when combined with azacitidine. But more research is needed to fully assess its approved used. We will post further updates as they are published. 

Maintenance therapy with venetoclax is still under investigation in the transplant setting. Potential benefits include prolonged remission and improved survival, but risks such as low blood counts from myelosuppression and infections must be carefully managed. Patients with certain high-risk genetic profiles, such as TP53 mutations, may particularly benefit, although relapse can still occur.

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Sources:

• Prophylactic maintenance with venetoclax/azacitidine after reduced-intensity conditioning allogeneic transplant for high-risk MDS and AML
• A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML) (VIALE-T)