In a single-institution phase I/II study reported in the Journal of Clinical Oncology, Courtney D. DiNardo, MD, and colleagues found that the combination of venetoclax with FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin) in induction and consolidation treatment was highly effective in patients with newly diagnosed acute myeloid leukemia (AML) and in those with relapsed/refractory AML.

Courtney D. DiNardo, MD

Study Details

To date, the study has enrolled a total of 68 patients at The University of Texas MD Anderson Cancer Center treated with induction and consolidation venetoclax plus FLAG-IDA, including 16 with relapsed/refractory AML in a venetoclax dose-escalation phase IB portion, 29 with newly diagnosed AML in a phase IIA portion, and 23 with relapsed/refractory AML in a phase IIB portion. Patients in the phase IB group received venetoclax at 200 mg or at the selected phase II dose of 400 mg. After completion of induction or consolidation, continuous daily venetoclax maintenance was permitted for patients not proceeding to hematopoietic stem cell transplantation (HSCT).

Key Findings

Overall response rates were 75% among patients with relapsed/refractory AML in the phase IB group, 97% among patients with newly diagnosed AML in the phase IIA group, and 70% among patients with relapsed/refractory AML in the phase IIB group. Rates of composite complete response (complete response, complete response with partial hematologic recovery, and complete response with incomplete hematologic recovery) were 75%, 90%, and 61%, respectively.

Measurable residual disease–negative composite complete response was achieved in 96% of patients with newly diagnosed AML and 69% of all patients with relapsed/refractory AML.

After a median follow-up of 12 months, median overall survival was 9 months (95% confidence interval [CI] = 4.9 months–not estimable) in the phase IB group, not reached (95% CI = not estimable–not estimable) in the phase IIA group, and not reached (95% CI = 6 months–not estimable) in the phase IIB group, with 12-month rates of 38%, 94%, and 68%, respectively.  

Overall, 56% of patients proceeded to allogeneic HSCT, including 69% of patients with newly diagnosed AML and 46% with relapsed/refractory AML. Overall survival at 12 months among patients with relapsed/refractory AML undergoing HSCT was 87%; a 3-month landmark analysis showed improved survival among those with vs without composite complete response (median = not reached vs 7 months [P = .009]). Post-HSCT 12-month overall survival was 94% in patients with newly diagnosed AML and 78% in those with relapsed/refractory AML.

Grade 3 and 4 adverse events occurring in ≥ 10% of patients included febrile neutropenia (50%), bacteremia (35%), pneumonia (28%), and sepsis (12%). Across all groups, 30- and 60-day mortality was 0% and 4.4%. Death on study or within 1 week of discontinuation occurred in six patients with relapsed/refractory AML; causes in four patients without response were sepsis in two, pneumonia in one, and pulmonary hemorrhage in one, and causes in two responding patients were sepsis in one and hemophagocytic syndrome in one.

The investigators concluded: “[FLAG-IDA plus] venetoclax represents an effective intensive treatment regimen in newly diagnosed AML and relapsed/refractory AML patients, associated with deep remissions and a high rate of transition to successful transplantation.”

Dr. DiNardo, of the Department of Leukemia, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by a Lloyd Family/V Foundation Clinical Scholar Award and by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.