Compared to Venetoclax Plus Hypomethylating Agents, High Dose Cytarabine Based Intensive Chemotherapy Induction for Newly Diagnosed Acute Myeloid Leukemia (AML) Leads to a Faster Remission Resulting in Better Survival

Hypomethylating agents plus venetoclax is a commonly used induction regimen for newly diagnosed AML patients who are not eligible for standard intensive chemotherapy (IC). Due to the high remission rates and the easier administration of Venetoclax plus hypomethylating agents in the outpatient settings and community practices, some patients receive such induction even if IC eligible. We retrospectively analyzed 206 newly diagnosed AML patients, age 56-80 years who received either Venetoclax plus hypomethylating agents (n=65) or high dose cytarabine based IC ( n=141) to assess the difference in remission rates, time to achieve remission and the impact of time to achieving remission on survival endpoints.

Patients who received IC ( FLAG or CLAG +/- Idarubicin) were younger ( median age 66 (56,79) vs 73(56,79) years, p<0.001) but had similar race distribution, NCCN cytogenetics risk and distribution of primary versus secondary leukemia compared to patients with hypomethylating agents plus venetoclax. Patients who received IC has similar chance of achieving CR (89% vs 71%, p=0.89) and transplant rate compared to venetoclax/hypomethylating agents. Patients who received IC had better DFS (p=0.026), a trend towards better OS (p=0.06) and similar relapse risk (p=0.69) compared to venetoclax/hypomethylating agents (figure 1). In a logistic regression analysis, patients who received IC and patients with favorable/intermediate risk AML had higher likelihood of achieving CR in the first 60 days post induction ( HR 2.34, 95% CI 1.19-4.61; P=0.01 for IC versus Venetoclax/hypometh; and HR 0.24 , 95% CI 0.12-0.49, P<0.001 for NCCN adverse versus favorable/intermediate risk AML). A cox model for survival endpoints where age was factored into three equal size groups (56-63, 64-70 and 71-79) and NCCN risk fitted as strata, was performed on survival endpoints. Achieving CR1 within 60 days of induction treatment had significant impact on overall survival (HR 0.24, 95% CI 0.13-0.46, p<0.001).

Our data shows that among patients aged 55-80 years with newly diagnosed AML, receiving high dose cytarabine based IC have similar rates but more likely to achieve CR within 60 days than venetoclax plus hypomethylating agents. Achieving CR within 60 days of induction is a predictor of better overall survival. Based on our analysis, high dose cytarabine based IC should remain the preferred choice for patients eligible for such treatment.