What is Core-binding Factor Acute Myeloid Leukemia (CBF-AML)?

Core-binding factor acute myeloid leukemia (CBF-AML) is a subtype of acute myeloid leukemia characterized by specific chromosomal translocations, such as t(8;21) and inv(16) [1, 3].

What were the findings of the phase 3 trial on dasatinib in CBF-AML?

The phase 3 trial (NCT02013648) showed that adding dasatinib to induction and consolidation therapy, followed by 12 months of maintenance, did not improve event-free survival (EFS) or overall survival (OS) compared to standard-of-care therapy for patients with CBF-AML.

What were the event-free survival (EFS) rates in the dasatinib and standard therapy arms?

The 4-year EFS rates were 44% in the dasatinib arm and 41% in the standard therapy arm (HR, 0.92; 95% CI, 0.63-1.33; P = .66).

What were the overall survival (OS) rates in the dasatinib and standard therapy arms?

The 4-year OS rates were 78% in the dasatinib arm and 76% in the standard therapy arm (HR, 0.93; 95% CI, 0.53-1.63; P = .79).

What were the complete remission (CR) rates in the dasatinib and standard therapy arms?

the complete remission (CR) rate was 55% in the dasatinib arm and 64.7% in the standard arm. The CR with incomplete hematologic recovery (CRi) was 36% in the dasatinib arm and 31.4% in the standard arm.

what were the most frequent serious adverse events in the dasatinib arm?

The most frequent serious adverse events in the dasatinib arm included pneumonia/pneumonitis, sepsis, febrile neutropenia, and pyrexia.

AML Treatment Could Soon Get an All-Oral Option

FDA is reviewing a drug combination for acute myeloid leukemia patients ineligible for intensive chemotherapy.

A potential new treatment option is on the horizon for acute myeloid leukemia (AML) patients who cannot undergo intensive induction chemotherapy. The FDA is currently reviewing a drug combination that could offer an all-oral alternative.

Key Development

The FDA has accepted a supplemental new drug application (sNDA) for decitabine and cedazuridine (Inqovi) plus venetoclax (Venclexta). This combination targets adult patients newly diagnosed with AML who are not candidates for intensive induction chemotherapy.

The sNDA submission relies on data obtained from the phase 2b ASCERTAIN-V trial (NCT04657081). The results were presented at the 2025 ASCO Annual Meeting and the 2025 EHA Congress.

ASCERTAIN-V assessed the efficacy of decitabine plus cedazuridine combined with venetoclax in 101 adult patients with newly diagnosed AML who were ineligible for intensive induction chemotherapy. After a median follow-up of 11.2 months, the trial achieved its primary endpoint, demonstrating a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%) across the entire group.

In addition, the CR/CR rate coupled with incomplete hematologic recovery reached 63.4% (95% CI, 53.2%-72.7%), and the CR/CR rate alongside partial hematologic recovery was 51.5% (95% CI, 41.3%-61.6%). The median overall survival was estimated at 15.5 months (95% CI, 7.6-not evaluable). At the one-year mark, the median duration of response was not reached, and 75.3% of patients who had achieved CR remained in CR.

Subgroup analyses revealed consistent CR rates across defined patient subgroups. High CR rates were seen in patients under 76 years old (57.9%; 95% CI, 33.5%-79.7%) and those with a baseline ECOG performance status of 0 (51.9%; 95% CI, 31.9%-71.3%). Among patients who had not received prior anticancer therapies, the CR rate stood at 48.8% (95% CI, 37.9%-59.9%).

“We have an unwavering dedication to developing innovative new cancer treatments, and the FDA’s acceptance of our sNDA for [decitabine plus cedazuridine] in combination with venetoclax highlights the need for novel approaches in AML,” stated Harold Keer, MD, PhD, chief medical officer of Taiho Oncology, in a news release.

Keer also noted, “If approved for patients with AML who are not eligible to undergo intensive induction chemotherapy, [decitabine plus cedazuridine] in combination with venetoclax would offer the first all-oral alternative to current therapies.”

Treatment Regimen and Safety Profile

During the ASCERTAIN-V trial, patients received decitabine plus cedazuridine on days 1 through 5 of each 28-day treatment cycle, along with daily venetoclax. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal.

Investigators reported no new safety concerns associated with the combination therapy. Overall, 99.0% of patients experienced adverse effects (AEs), 80.2% experienced treatment-related AEs, 84.2% experienced serious AEs, and 35.6% experienced treatment-related serious AEs. Grade 3 or higher AEs were seen in 98.0% of patients, with febrile neutropenia (49.5%), anemia (38.6%), and neutropenia (35.6%) being the most common.

Other grade 3 or higher AEs included decreased platelet counts (24.8%), thrombocytopenia (19.8%), decreased neutrophil count (19.8%), decreased white blood cell counts (14.9%), and decreased appetite (1.0%). AEs led to treatment discontinuation (8.9%), treatment interruption (68.3%), and dose reduction (13.9%). Within 30 days of the first dose, 3 deaths were linked to AEs or disease progression; this number increased to 10 deaths within 60 days.

Pharmacokinetic analyses confirmed the absence of drug-drug interactions between decitabine/cedazuridine and venetoclax. Furthermore, venetoclax did not affect the pharmacokinetics of decitabine and cedazuridine.

Decitabine/Cedazuridine Plus Venetoclax in AML | Image Credit: © LELISAT – stock.adobe.com

Previous Approvals

The FDA previously approved decitabine plus cedazuridine in July 2020 for treating adult patients with specific subtypes of previously untreated de novo and secondary myelodysplastic syndromes, including chronic myelomonocytic leukemia.

In the United States, it is estimated that 6,000 new cases of AML will be diagnosed in 2024, with most patients being over 60 years old (American Cancer Society).

Dasatinib Fails to Improve Outcomes in Core-Binding Factor Acute Myeloid Leukemia: Phase 3 trial Results

Milan, Italy – A recent phase 3 clinical trial has cast doubt on the effectiveness of dasatinib, a tyrosine kinase inhibitor, as an addition to standard chemotherapy for patients with core-binding factor acute myeloid leukemia (CBF-AML). the study, presented at the 2025 European Hematology association (EHA) Congress, revealed that the addition of dasatinib to induction and consolidation therapy, followed by 12 months of maintenance, did not considerably improve event-free survival (EFS) or overall survival (OS) compared to standard treatment protocols.

dasatinib’s Role in CBF-AML Treatment questioned

The multi-center,randomized trial enrolled 204 patients with CBF-AML between August 2014 and February 2021. participants were assigned to either a standard therapy arm or an arm that included dasatinib in addition to standard chemotherapy. the primary endpoints were EFS and OS. The results indicated that the addition of dasatinib did not provide a statistically notable benefit in either EFS or OS.

Hartmut Döhner, MD, from the University Hospital Ulm in Germany, presented the findings, stating that the data “do not support the encouraging data reported in single-arm phase 2 studies,” emphasizing the necessity of rigorous investigation of new agents in controlled, randomized trials.

Did You know? Core-binding factor AML accounts for approximately 10-15% of all AML cases,and is often associated with favorable outcomes with standard chemotherapy American Cancer Society.

Key Trial Results: A Side-by-Side Comparison

The trial data revealed the following outcomes:

Outcome	Standard Therapy Arm (n = 102)	Dasatinib Arm (n = 100)
4-Year event-Free Survival (EFS)	41%	44%
4-year Overall Survival (OS)	76%	78%
Complete Remission (CR) Rate	64.7%	55%
CR with Incomplete Hematologic Recovery (CRi)	31.4%	36%
30-Day Mortality Rate	2%	3%

Adverse Events and Tolerability

While the addition of dasatinib did not improve survival outcomes, it was associated with a higher incidence of certain adverse events (AEs). Hematologic AEs such as leukopenia were more frequent in the dasatinib arm (91% vs. 79%; P = .02). Non-hematologic AEs, including atrial fibrillation (0% vs. 4%; P = .04) and colitis (1% vs. 8%; P = .02), were also more common in the dasatinib arm.

Serious AEs were reported in 64% of patients in the dasatinib arm compared to 36% in the standard arm, with pneumonia/pneumonitis, sepsis, febrile neutropenia, and pyrexia being the most frequent.

Pro Tip: When evaluating cancer treatment options, it’s crucial to consider both the potential benefits and the risks of adverse events.

acute myeloid leukemia

Decitabine/Cedazuridine Plus Venetoclax sNDA Under FDA Review for Newly Diagnosed AML