Venetoclax Plus LDAC May Benefit Patients with AML Ineligible for Intensive Chemotherapy

The combination of venetoclax and low-dose cytarabine (LDAC) appears to be well-tolerated and is associated with high rates of remission in patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, found a new study published in the Journal of Clinical Oncology.

Andrew H. Wei, of The Alfred Hospital and Monash University, Melbourne, Australia, and colleagues conducted an international phase Ib/II study examining the safety and efficacy of the selective B-cell leukemia/lymphoma-2 inhibitor venetoclax plus LDAC. A total of 82 adults aged 60 years or older (median age, 74 years) with previously untreated AML ineligible for intensive chemotherapy were evaluated. Individuals who received prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), were included. The patients received venetoclax 600 mg per day orally in 28-day cycles, and subcutaneous LDAC (20 mg/m² per day) on days 1 to 10.

The study showed that 54% of patients achieved complete remission with incomplete blood count recovery (CRi). The median time to first response was 1.4 months, the median overall survival (OS) was 10.1 months, and the median duration of response (DOR) was 8.1 months (range, 5.3–14.9 months). When the researchers separately analyzed patients without prior HMA exposure, CR/CRi was achieved in 62%, the median duration of respomse was significantly longer (14.8 months), and the median OS was significantly longer (13.5 months; range,7.0–18.4 months).

“High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy,” concluded the authors.  

Chetasi Talati, MD, who is an assistant member of Moffitt Cancer Center’s Department of Malignant Hematology, Tampa, Florida, said this study is important because prior history of myelodysplastic syndrome was included along with prior treatment with hypomethylating agents. “Traditionally, this subgroup of patients do[es] not have great responses with shortened overall survival,” said Talati. “Median overall survival was considerably longer at 10.1 months compared to historical cohorts of such disease characteristics.”

Patients with poor-risk cytogenetic profiles had combined CR/CRi rates of 42%, which is significant because such patients do not usually respond well to conventional therapies and typically have inherently resistant disease, she said. “There were 10 patients enrolled on the study that harbored TP53 mutation, and response rate was noted to be 30% in this adverse-risk subgroup,” Talati told Cancer Network.

The overall 30-day mortality rate was 6% in this study. Grade 3 or higher febrile neutropenia and thrombocytopenia occurred in 42% and 38% of patients, respectively. Neutropenia occurred in 27% of patients, and anemia occurred in 27% of patients as well. Common nonhematologic adverse events of any grade included nausea (70%), diarrhea (49%), hypokalemia (48%), and fatigue (43%).

“Close monitoring and robust supportive care measures are extremely necessary when administering this treatment until response is achieved. It is also important to be vigilant about appropriate venetoclax dose reductions with concomitant CYP3A inhibitors,” said Talati.