|The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Hematology Advisor’s conference coverage.|
The addition of venetoclax to low-dose cytarabine (LDAC) improved overall survival (OS) compared with placebo and LDAC among older patients with acute myeloid leukemia (AML) and among patients with AML who had comorbidities that made them ineligible for intense chemotherapy, according to results of a phase 3 trial presented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.
“Results from early-phase studies led to a phase 3 trial called VIALE-C,” Andrew H. Wei, MD of the Alfred Hospital and Monash University in Australia, and lead author and presenter of the study, said. “The primary analysis of this study showed a 25% reduction in the risk of death with venetoclax in combination with LDAC,” he said. This updated analysis includes an additional 6 months of data, where there was found to be a 30% reduction in the risk of death with the venetoclax combination.
The double-blind phase 3 VIALE-C trial randomly assigned 211 patients with previously untreated AML 2:1 to receive venetoclax plus LDAC or placebo plus LDAC. All patients were 75 years or older or had comorbidities that made them ineligible for intense chemotherapy. The primary endpoint was OS. Secondary endpoints included response, event-free survival (EFS), and transfusion dependence.
At baseline, the median patient age was 76 years, and 56% of patients were male. AML was secondary in 38% of patients, 20% had received a prior hypomethylating agent, and 32% had poor cytogenetic risk.
During a median follow-up of 17.5 months, venetoclax significantly prolonged OS, with a median OS of 8.4 months compared with 4.1 months with placebo (hazard ratio [HR], 0.70; 95% CI, 0.50-0.99; P =.04). Median EFS was 4.9 months with venetoclax compared with 2.1 months with placebo (HR, 0.61; 95% CI, 0.44-0.84; P =.003).
Response rates were also higher with venetoclax. The complete remission (CR) was 28% with venetoclax compared with 7% with placebo (P <.001) with a median duration of 17 or 8 months, respectively. The CR/CR with incomplete blood count recovery was 48% with venetoclax compared with 13% with placebo (P <.001) with a median duration of 12 or 6 months, respectively. The CR/CR with partial hematologic recovery was 48% and 15% with venetoclax or placebo, respectively (P <.001).
Transfusion dependence from red blood cell/platelets was 43%/49% with venetoclax compared with 19%/32% with placebo (P <.001/P =.024).
Rates of adverse events (AEs) were generally similar between groups, except several grade 3 or higher AEs that occurred more frequently with venetoclax compared with placebo, which included neutropenia, thrombocytopenia, and febrile neutropenia. Treatment discontinuation due to AEs and not related to progressive disease occurred in 11% and 9% of patients in the venetoclax and placebo arms, respectively.
Dr Wei said that these results suggest that “venetoclax plus LDAC represents a clinically important therapeutic option for this underserved AML patient population.”
Wei AH, Montesinos P, Ivanov V, et al. A phase 3 study of venetoclax plus low-dose cytarabine in previously untreated older patients with acute myeloid leukemia (VIALE-C): a 6-month update. Paper Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S136.
This article originally appeared on Cancer Therapy Advisor