ASH 2022: Final Results of the VIALE-A Trial

ASH 2022: Final Results of the VIALE-A Trial Assessing Venetoclax Plus Azacitidine

Posted: Dec 12, 2022

Venetoclax is a promising BCL-2 inhibitor currently used in combination with other therapies to treat AML. Venetoclax shuts down BCL-2 which is an anti-apoptotic protein, meaning it stops cells from dying. Leukemia cells make this protein, so shutting it down kills the cancer cells.

Due to the results of the phase 3 VIALE-A study published in 2020, venetoclax and azacitidine were approved by the FDA and can now be used together to treat newly diagnosed AML patients who can't get intensive chemotherapy. After two more years of follow-up, during which all 360 of the expected survival events were measured, AML expert, Dr. Pratz, discussed the study's final results at the 64th Annual Meeting of the American Society of Hematology (ASH 2022).

Methods and Patients Included in the Study

The median age was 76 years in both groups, 60% were men and 76% were Caucasians.

A total of 431 untreated AML patients ineligible for intensive chemotherapy
ARM: Venetoclax + Azacitidine	ARM: Placebo + Azacitidine
286 patients	145 patients
Oral 400 mg Venetoclax daily, 28-day cycles	Oral Placebo daily, 28-day cycles
Azacitidine was administered to all patients at the standard dose: 75 mg/m2 subcutaneously or intravenously on days 1 through 7 every 28-day cycle

Molecular Abnormalities	Patients with Venetoclax+Azacitidine
FLT3	14.1%
IDH1/2	24.9%
TP53	23.3%
NPM1	16.6%

Study Results

After a median of 43.2 months of follow-up, 49 patients remained in the study: 28 in the venetoclax group and 1 in the placebo group. The results of the study showed a clear benefit for the combination of venetoclax and azacitidine over azacitidine alone.

The outcomes were as follows:

Group Type	Groups	Patients	Median Overall Survival (OS)
All Patients (Figure 1)	Venetoclax and Azacitidine	286	14.7 months (12.1 - 18.7)
All Patients (Figure 1)	Placebo and Azacitidine	145	9.6 months (7.4 - 12.7)
Patients that achieved CR+CRi and MRD negative 10^-3	Venetoclax and Azacitidine	69 of 286	34.2 months (27.7 - 44)
Patients that achieved CR+CRi and MRD negative 10^-3	Placebo and Azacitidine	11 of 145	25 months (7 - 39.8)
Patients that achieved CR+CRi and MRD positive 10^-3	Venetoclax and Azacitidine	96 of 286	18.7 months (12.9 - 23.5)
Patients that achieved CR+CRi and MRD positive 10^-3	Placebo and Azacitidine	24 of 145	15.1 months (7.4 - 26.1)
Patients in the IDH1/2 mutant subgroup (Figure 2)	Venetoclax and Azacitidine	61 of 286	19.9 months (12.2 - 27.7)
Patients in the IDH1/2 mutant subgroup (Figure 2)	Placebo and Azacitidine	28 of 145	6.2 months (2.3 - 12.7)

Figure 1. Overall survival. This graph shows a sustained benefit of using venetoclax and azacitidine after 43.2 months of follow-up.
Figure 2. Overall survival of the IDH/2 mutant group. This graph shows an even more significant sustained benefit of using venetoclax and azacitidine for patients that have an IDH1/2 mutation after 43.2 months of follow-up.

Side Effects

Side Effect	Grade	Groups	Patients affected
Nausea	Any	Venetoclax and Azacitidine	44.5%
Nausea	Any	Placebo and Azacitidine	36.8%
Diarrhea	Any	Venetoclax and Azacitidine	45.2%
Diarrhea	Any	Placebo and Azacitidine	34%
Constipation	Any	Venetoclax and Azacitidine	43.8%
Constipation	Any	Placebo and Azacitidine	18.8%
Low Platelets	≥ 3	Venetoclax and Azacitidine	45.9%
Low Platelets	≥ 3	Placebo and Azacitidine	39.6%
Low Neutrophils	≥ 3	Venetoclax and Azacitidine	42.8%
Low Neutrophils	≥ 3	Placebo and Azacitidine	28.5%
Fever due to Low Neutrophils	≥ 3	Venetoclax and Azacitidine	42.8%
Fever due to Low Neutrophils	≥ 3	Placebo and Azacitidine	18.8%
Any serious adverse event		Venetoclax and Azacitidine	85.1%
Any serious adverse event		Placebo and Azacitidine	77.1%

Take Away Points

The long-term follow-up of VIALE-A shows that venetoclax and azacitidine are better in terms of overall survival (14.7 months), than Placebo and Azacitidine (9.6 months) in all subgroups of AML patients who are not eligible for intensive chemotherapy.
Those patients in the ventoclax group that were MRD negative 10^-3 who had achieved a complete response had an improved 34.2 months overall survival, and patients with IDH1/2 mutations treated had an improved overall survival of was 19.9 months.
The VIALE-A 2-year follow-up analysis confirms the long-term survival benefit for patients treated with venetoclax and azacitidine, with no new side effects.

For more information about this clinical trial, click here.

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about the author
Arturo Hurtado

Arturo Hurtado is an International Medical Graduate who joined HealthTree in 2020 as part of the Patient Experience team. He helps patients understand their disease panorama and navigate their AML through the tools and resources that HealthTree provides. He is an enthusiastic photographer, tech nerd, and aspiring food explorer who loves to travel and find new exciting experiences.