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. 2021 Dec 28;5(24):5565-5573.
doi: 10.1182/bloodadvances.2021005538.

Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia

Evan M Cherry  1 , Diana Abbott  2 , Maria Amaya  1 , Christine McMahon  1 , Marc Schwartz  1 , Julie Rosser  3 , Audrey Sato  3 , Jeffrey Schowinsky  3 , Anagha Inguva  1 , Mohd Minhajuddin  1 , Shanshan Pei  1 , Brett Stevens  1 , Amanda Winters  1 , Craig T Jordan  1 , Clayton Smith  1 , Jonathan A Gutman  1 , Daniel A Pollyea  1
Affiliations

Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia

Evan M Cherry et al. Blood Adv. .

Abstract

Venetoclax (ven) plus azacitidine (aza) is the standard of care for patients with newly diagnosed acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (IC). Some patients who are IC candidates instead receive ven/aza. We retrospectively analyzed patients with newly diagnosed AML who received ven/aza (n = 143) or IC (n = 149) to compare outcomes, seek variables that could predict response to 1 therapy or the other, and ascertain whether treatment recommendations could be refined. The response rates were 76.9% for ven/aza and 70.5% for IC. The median overall survival (OS) was 884 days for IC compared with 483 days for ven/aza (P = .0020). A propensity-matched cohort was used to compare outcomes in the setting of equivalent baseline variables, and when matched for age, biological risk, and transplantation, the median OS was 705 days for IC compared with not reached for ven/aza (P = .0667). Variables that favored response to ven/aza over IC included older age, secondary AML, and RUNX1 mutations. AML M5 favored response to IC over ven/aza. In the propensity-matched cohort analyzing OS, older age, adverse risk, and RUNX1 mutations favored ven/aza over IC, whereas intermediate risk favored IC over ven/aza. In conclusion, patients receiving IC have improved OS compared with those receiving ven/aza. However, in a propensity-matched cohort of patients with equivalent baseline factors, there was a trend toward favorable OS for ven/aza. Specific variables, such as RUNX1 mutations, reported here for the first time, can be identified that favor ven/aza or IC, helping to guide treatment decisions for patients who may be eligible candidates for either therapy.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS and PFS analyses of patients who received IC or ven/aza. Median OS (A) and PFS (B) of patients who received ven/aza (red) vs those who received IC (blue). In a cohort of patients propensity matched for age, ELN risk group, and transplantation status, median OS (C) and PFS (D) of patients who received ven/aza (red) vs those who received IC (blue).
Figure 2.
Figure 2.
Predictive value of baseline variables for favoring IC or ven/aza. (A) Factors that favored the likelihood of achieving a response (CR or CRi) to IC vs ven/aza. RUNX1 mutation plus age ≥65 years was assessed but not estimable. (B) Factors that favored OS for IC compared with ven/aza. (C) In a cohort of patients propensity matched for age, ELN risk group, and transplantation status, factors that favored OS for IC vs ven/aza. Variables that were assessed but not estimable included NPM1 mutation plus age ≥65 years and RUNX1 mutation plus age ≥65 years.
Figure 2.
Figure 2.
Predictive value of baseline variables for favoring IC or ven/aza. (A) Factors that favored the likelihood of achieving a response (CR or CRi) to IC vs ven/aza. RUNX1 mutation plus age ≥65 years was assessed but not estimable. (B) Factors that favored OS for IC compared with ven/aza. (C) In a cohort of patients propensity matched for age, ELN risk group, and transplantation status, factors that favored OS for IC vs ven/aza. Variables that were assessed but not estimable included NPM1 mutation plus age ≥65 years and RUNX1 mutation plus age ≥65 years.
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