Although azacitidine (Vidaza) combined with venetoclax (Venclexta) significantly improved response rates and overall survival (OS) in older, unfit patients with previously untreated acute myeloid leukemia (AML) compared with azacitidine alone, the two-drug regimen is not cost effective, according to Yale researchers.

The combination is recommended as standard-of-care for frontline therapy in this patient population based on data from the VIALE-A clinical trials.

To examine if the regimen was financially beneficial, the researchers developed a cost-effectiveness model comparing azacitidine/venetoclax with azacitidine alone. The patient population mirrored the recent phase 3 VIALE-A trial — median age was 76 years, 60% were men, and 37% had poor cytogenetic risk status. In addition, all patients were not eligible for standard induction therapy because of older age or comorbidities. More than half (55%) of patients had an ECOG performance status of 0 to 1, and 45% had a status of 2 to 3. IDH1/2 or FLT3 mutations were seen in both groups of patients.

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Their findings, which were published in Blood Advances, showed that azacitidine/venetoclax was associated with an improvement of 0.61 quality adjusted life-years (QALYs) vs azacitidine alone (1.53 vs 0.91 QALYs, respectively). But with that benefit also came higher lifetime healthcare costs than azacitidine alone — $491,093 vs $331,498, respectively.

“The incremental cost-effectiveness ratio azacitidine/venetoclax was $260,343 per QALY, which is above the willingness-to-pay threshold of $150,000 per QALY,” the researchers wrote.

The model factored in costs for oral medications, outpatient physician follow-up, transfusion support, best supportive care, end-of-life care, and hospitalization.

To make the azacitidine/venetoclax combination cost-effective for the older, unfit population, the monthly cost of venetoclax would need to be reduced by 60%, concluded the researchers.

Another way to increase the economic value of venetoclax would be to [safely] reduce the dosage. For example, the researchers stated that several studies reported concurrent use of venetoclax and CYP450 inhibitors only required a dose as low as 50 mg compared with the standard 400 mg dose. In addition, the monthly cost of venetoclax went from $12,000 to $3,000 when the dosage was lowered from 400 mg to 100 mg, as the researchers stated in their analysis.

Despite these findings, limitations to the study included availability of data used to populate the model, the ability to accurately model the costs of the postprogression health state because data regarding receipt of second-line treatment was not reported in the VIALE-A study, variations in provider practice regarding venetoclax administration, and the inability to use direct patient-reported outcomes from the VIALE-A trial because they were not available.

Disclosure: Some authors declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Patel KK, Zeidan AM, Shallis RM, et al. Cost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia. Blood Adv. 2021;5(4):994-1002. doi:10.1182/bloodadvances.2020003902