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

Abstract

Venetoclax (ven) + azacitidine (aza) is the standard of care for newly-diagnosed acute myeloid leukemia (AML) patients who are not candidates for intensive chemotherapy (IC). Some patients who are IC candidates instead receive ven/aza. We retrospectively analyzed newly-diagnosed AML patients who received ven/aza (N=143) or IC (N=149), to compare outcomes and seek variables that could predict response to one or the other therapy, and ascertain whether treatment recommendations can be refined. The response rate for ven/aza was 76.9% and 70.5% for IC. The median overall survival (OS) for IC was 884 days compared to 483 for ven/aza (p=0.0020). A propensity-matched cohort was utilized 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 and not reached for ven/aza (p=0.0667). 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, while intermediate risk favored IC over ven/aza. In conclusion, IC patients have improved OS compared to ven/aza. However, in a propensity-matched cohort of patients with equivalent baseline factors, there was a trend toward a favorable OS for ven/aza. Specific variables, such as reported here for the first time RUNX1 mutations, can be identified that favor ven/aza or IC, helping to guide treatment decisions for patients who may be eligible candidates for either therapy.

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

“…Other single center studies have shown similar outcomes as our study including Salhotra et al 34 (mOS, 11 vs 10 months for ven/aza vs CPX-351, respectively; P = .76) in 50 patients at City of Hope, and Asghari et al 35 (mOS, 14 vs 11 months for ven/aza vs CPX-351, respectively; P = .82) in 199 patients at Moffitt Cancer Center and Memorial Healthcare System. Other efforts to compare venetoclax and HMA with intensive chemotherapy are also emerging and require careful comparison, or adjustment, of baseline characteristics to overcome confounding by indication 14 and rate of transplant in both groups. This study was not designed to assess the impact of initial treatment on transplant.…”

“…There is emerging evidence of successful allogeneic transplant after initial treatment with ven/aza, 13 and recent observational studies comparing venetoclax and azacitidine to 7 + 3 also show similar survival with transplant. 14 Comparative data for CPX-351 vs ven/aza is lacking. Clinicians often rely on local practice patterns, hypotheses about molecular subsets that may benefit from 1 type of treatment, or other subjective factors to choose induction therapy.…”

New Therapeutic Strategies for Adult Acute Myeloid Leukemia

“…Venetoclax has been shown to be effective against AML with IDH1/IDH2 or RUNX1 mutations in vitro. This was confirmed in the Viale-A study, and in another retrospective study which showed that IDH and RUNX1 mutations were predictors of treatment response after combination therapy with venetoclax and AZA [ 16 , 94 , 95 ]. Although VEN is considered to be an alternative to conventional cytotoxic chemotherapy for unfit AML patients, more cases must be examined to determine whether VEN is a viable alternative to the so-called ‘3 + 7′ in fit AML patients.…”

Methylation of SPRED1: A New Target in Acute Myeloid Leukemia

“…Therefore, we determined the demethylation influence on cell lines with bisulfite modification, followed by PCR and sequencing, which is the most effective method for the high-resolution methylation mapping of genomes ( 28 ). As a DNA methyltransferase inhibitor, 5-AZA is a clinically used epigenetic agent that induces promoter demethylation and gene re-expression AML ( 29 , 30 ). It confirmed that the methylation level of SPERD1 is negatively correlated with mRNA or protein level, and after treatment of 5-AZA, the mRNA and protein levels of SPRED1 increased significantly.…”