Venetoclax Added to Intensive Chemotherapy Is Safe, Effective in Relapsed/Refractory AML

In a study presented at EHA2021 Virtual, the annual congress of the European Hematology Association, adding short-term venetoclax to an intensive FLA-IDA chemotherapy regimen proved safe and led to high rates of overall response (ORRs) and measurable residual disease (MRD) negativity in patients with relapsed/refractory acute myeloid leukemia (AML). The findings were shared by Rabia Shahswar, MD, of Hannover Medical School in Germany. 

Noting the limited treatment options for patients in this setting, Dr. Shahswar and researchers conducted a retrospective controlled study to evaluate the FLAVIDA combination (the BCL2 inhibitor venetoclax plus fludarabine, cytarabine, and idarubicin) in patients with relapsed/refractory AML. 

Thirty patients (median age = 54 years) were included in the analysis. One-third of patients had secondary or therapy-related AML, and most patients (57%) had intermediate-risk disease. Patients received a seven-day course of venetoclax 100 mg, along with standard intensive FLA-IDA chemotherapy. Patients received a maximum of one course FLAVIDA. 

The ORR was 73% (n=22/30), which included 18 patients (60%) who achieved a complete response (CR) or CR with incomplete hematologic recovery (CRi). Responses were seen across patients with different disease risk levels (75% for favorable, 71% for intermediate, and 78% for adverse). Four patients underwent allogeneic hematopoietic cell transplantation (alloHCT) before blood count recovery and achieved CR only after transplant, the researchers reported. 

Approximately half of responding patients with known molecular MRD markers achieved molecular MRD negativity (47%; n=8/17). 

One patient died before response assessment. Nineteen patients (63%) were consolidated with alloHCT, four received chemotherapy, three received donor lymphocyte infusions, and four received no additional treatment, Dr. Shahswar added. 

After a median follow up of 13.3 months, the median overall survival (OS) and event-free survival (EFS) in the group were 12 months and 9.5 months, respectively. Median relapse-free survival in patients who achieved CR/CRi was not reached. Survival outcomes were better for patients who reached MRD negativity, the researchers reported: 

  • median OS: not reached for MRD-negative vs. 11.3 months for MRD-positive (p=0.048) 
  • median EFS: not reached for MRD-negative vs. 9.5 months for MRD-positive (p=0.038) 

The most common grade 3/4 adverse events were neutropenic fever (71%) and bacteremia (32%), but the authors concluded that short-term venetoclax could be safely administered in combination with FLA-IDA in younger, fit patients with AML. The findings from this report are promising, they concluded, although they are limited by the small patient population. 

Study authors report no relevant conflicts of interest. 


Shahswar R, Beutel G, Gabdoulline R, et al. FLAVIDA chemotherapy induces MRD-negative remission in patients with relapsed/refractory acute myeloid leukemia. Abstract #S139. Presented at the EHA2021 Virtual Congress, June 9-17, 2021.