Changing Frontline AML Treatment Patterns in Alberta, Canada from 2013 - 2022

Acute myeloid leukemia (AML) is most commonly treated with intensive induction chemotherapy (IT). Older patients who are unfit for intensive therapies due to co-morbidities and/or frailty are offered non-intensive palliative chemotherapy (NIT), while some patients receive only best supportive care (BSC). As a result of the Viale A study¹, the combination of azacitidine + venetoclax (aza-ven) has recently become the standard NIT treatment option. However, the impact of this new therapy on AML treatment patterns in a real-world setting has not been clearly delineated.

Methods: The University of Alberta Hospital (UAH) is the sole acute leukemia referral and treatment center for northern Alberta, Canada, serving around 2 million people. All newly diagnosed AML patients presenting to UAH from January 2021 to June 2022 were analyzed, and compared to a similar cohort of all new AML patients presenting to the same center between Jan. 2013 - Dec. 2016. From this, we performed retrospective chart reviews to obtain demographic, diagnostic, treatment, and outcome data. Prior approval was obtained from the provincial Cancer IRB. Treatment protocols were relatively uniform and adhered to by all treating leukemia physicians at the center.

Patients selected for IT usually received induction with a 7+3 regimen of cytarabine plus idarubicin. Patients deemed unfit for IT were offered NIT: In the 2013-16 cohort, this generally consisted of monotherapy with azacitidine or low-dose cytarabine (LDAC). Of NIT patients in the 2021-22 cohort, 79% received aza-ven, 9% received LDAC-ven and 12% received either azacitidine or LDAC monotherapy. The no therapy (NT) group included those who received only BSC +/- hydroxyurea, or who died before any treatment could be administered.

Results: The median age, sex, cytogenetic risk group, de novo vs. secondary AML, location (urban vs rural) and other baseline characteristics were not significantly different between the two cohorts. Of 316 patients presenting between 2013-16, 50.3% received IT, 24.7% NIT and 25% NT. Of 115 patients presenting from 2021-22, 47% received IT, 33.9% NIT and 19.1% NT. Amongst the patients age < 60 and 60-69 years, there was no significant difference in the proportion of patients receiving IT, NIT and NT between the 2013-16 and 2021-22 cohorts. Amongst patient age 70 and older, the proportion of patients in the 2013-16 cohort receiving IT, NIT and NT were 10.3%, 44.1% and 45.5%, respectively. In comparison, the proportion of patients in the 2021-22 cohort receiving IT, NIT and NT were 5.7%, 64.1% and 30.2%, respectively (P=0.018 by Chi square, comparing the two cohorts).

Within the 70-79 age group, the proportion of patients receiving NIT increased from 46.5% in 2013-16 to 66.7% in 2021-22, while the proportion receiving NT decreased from 36% to 23%. Similarly, in the 80+ age group the proportion receivjng NIT increased from 40.7% to 59.1% and the proportion receiving NT decreased from 59.1% to 40.1%. The CR/CRi rate in the entire NIT group increased from 28% in 2013-16 to 50% (58% for those who received aza-ven) in 2021-22.

Conclusion: In a real-world setting there has been a significant increase in the proportion of patients age 70 and older receiving NIT in 2021-22 as compared with 2013-16, with a corresponding decrease in the proportion receiving both IT and NT. While further evaluation is needed to determine the reasons, it may be related to the availability of more effective venetoclax-based regimens influencing treatment decisions. More follow-up is needed to evaluate the overall effect on survival in these older patients.

Ref 1: DiNardo CD et al. N Engl J Med. 2020;383(7):617-29.

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