Venetoclax Plus “7+3” Chemotherapy: A Promising Induction Therapy for Newly Diagnosed AML

A groundbreaking study that could potentially change the standard of care treatments for newly diagnosed acute myeloid leukemia (AML) was presented at this year’s American Society of Hematology (ASH) meeting. 

Study Overview

A new Phase 1b clinical trial is showing encouraging results for patients with newly diagnosed acute myeloid leukemia (AML). The trial, led by Dr. Ioannis Mantzaris at a tertiary academic center, evaluated the safety and effectiveness of adding venetoclax (Venclexta, Abbvie) to the standard “7+3” chemotherapy regimen, which includes daunorubicin and cytarabine.

“We’ve been trying to improve upon the results that 7+3 alone has produced for years in [acute myeloid leukemia],” shares Dr. Ioannis Mantzaris, the trial’s primary investigator, “by the addition of venetoclax.”

Venetoclax has been highly successful in older, frail AML patients who may not tolerate intensive chemotherapy. Seeing this success, Dr. Mantzaris and his research team wanted to determine whether venetoclax could also improve outcomes in younger, fit patients in earlier stages of the disease.

Watch the interview below to hear the primary investigator, Dr. Mantzaris, discuss this promising approach, including why they chose to add venetoclax to an already successful regimen and why he’s excited about the future of AML treatment.

Key Objectives

The trial set out to answer two main questions:

1. Primary Objective: What is the optimal duration of venetoclax when combined with “7+3” chemotherapy?

2. Secondary Objectives: How well does this combination work, based on remission rates, survival outcomes, and duration of remission?

Additionally, the team wanted to understand if adding venetoclax would introduce any new toxicities.

How the Study Worked

To balance safety and effectiveness, venetoclax was tested at three durations: 8, 11, and 14 days. Since there is no universal standard for venetoclax dosing, the trial used a dose-escalation approach to identify the safest and most effective duration.

• Chemotherapy Regimen:

• Daunorubicin (60 mg/m² for patients ≤60 years)

• Cytarabine (100 mg/m² on days 2-8)

• Consolidation Therapy: Venetoclax (fixed dose) and intermediate-dose cytarabine, adjusted for age.

Results

Patient Demographics

The trial enrolled 34 patients, separated into younger (≤60 years) and older (>60 years) cohorts.

• Total Patients: 34 (20 younger, 14 older)

• Median Age: 59 years (range: 27-71)

• 62% were from ethnic/racial minority groups.

Safety Findings

The combination of venetoclax and “7+3” chemotherapy was well-tolerated, with no unexpected toxicities.

• No dose-limiting toxicities (DLTs) were observed.

• Most common side effects:

• Low white blood cell counts (neutropenia) with fever was observed in all patients treated

• Sepsis was reported in 24% of patients

• Enterocolitis or inflammation of the colon (24% of patients)

• No patients passed away during induction therapy.

Efficacy Results

The trial showed a significant signal of efficacy, with high remission rates and deep responses:

• 85% of patients achieved complete remission (CR) or CR with partial hematologic recovery.

• 86% were MRD-negative, indicating deep remission beyond what standard tests can detect.

“We saw a significant response signal,” explains Dr. Mantzaris. However, he cautions that these findings come from a small, early-phase trial, and larger randomized studies will be needed to confirm these results.

Response Outcomes

After half of the patients had been in the study for at least 9.6 months:

• 64% are in continuous MRD-negative remission.

• 29% underwent stem cell transplantation in their first remission.

• More than 50% of patients haven’t shown any signs of progressive disease.

Patient Perspectives 

Steve Hodges, AML Patient and HealthTree Coach shares his personal experience with this treatment regimen: 

“As an AML patient who went through 7+3, then FLAG, then two of the usual consolidations, I yet found myself with minimal residual disease (MRD) and the presence of remaining mutations of concern, including RUNX1. In consultation with my excellent oncologist at Duke (Dr. Thomas LeBlanc) and being fit despite the chemo, we decided to add two cycles of venetoclax with azacitidine. I’d not had venetoclax beforehand. 

The venetoclax cycles eliminated evidence of MRD from my resulting bone marrow biopsy, and I proceeded to get an allogeneic transplant from my son (haplo). At 20 months since the transplant, I am still in remission with no evidence of return, which probably would not have been the case had we not applied the two cycles of venetoclax. It is very exciting to see Dr. Mantzaris’s research from the recent ASH conference. It speaks to the amazing [potential for] venetoclax in consolidation similar to what I had and provides hope for many.”

Conclusions

This study provides early evidence that combining venetoclax with “7+3” chemotherapy is not only safe but highly effective in inducing deep remissions in newly diagnosed AML patients. Importantly, these promising outcomes were observed without added toxicity.

The next step is to determine the optimal duration of venetoclax (8 vs. 14 days) in a larger Phase II trial, sponsored by the National Cancer Institute (NCI).

“I think it’s going to be one of the therapeutic alternatives for the future,” Dr. Mantzaris suggests. “Maybe it will [even] challenge the current standard of care.”

As this research progresses, venetoclax-based therapies may open the door to new, more effective treatment strategies for AML patients worldwide.

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