The addition of venetoclax to fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) appears to demonstrate efficacy across acute myeloid leukemia (AML) subgroups and appears to have an acceptable safety profile, according to the results of an interim analysis of a phase 1b/2 study presented by Curtis Lachowiez, MD, of the University of Texas MD Anderson Cancer Center, in Houston, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“[In newly diagnosed AML], FLAG-IDA is associated with improved overall survival secondary to a decreased risk for relapse and is associated with low early death. In the relapsed/refractory population, however, we continue to see suboptimal outcomes with FLAG-IDA therapy,” said Dr Lachowiez.
Adult patients with treatment-naive/newly diagnosed or relapsed/refractory (R/R) AML were included in the study. Following the phase 1b (P1b) dose-escalation phase of the study, updated analysis of the phase 2 dose expansion also included an arm for each patient population: arm A (P2A) for newly diagnosed AML and arm B (P2B) for R/R AML.1,2
Overall, 68 patients completed at least 1 cycle of therapy prior to analysis; median number of cycles was 2 (range, 1-6) and was similar across the arms. Median age across all cohorts was 46 years (range, 20-73); median ages were 45 years (range, 20-65) in the P2A newly diagnosed AML arm, 51 years (range 20-73) in the P1b R/R arm, and 47 years (22-66) in the P2B R/R arm.
Patients with R/R AML had received a median of 2 prior lines of induction therapy (range 1-6) in the P1b arm and 1 (range 1-3) prior line of induction therapy in the P2B arm. Additionally, 50% of patients in the P1b arm and 30% of patients in the P2B arm underwent prior allogeneic hematopoietic stem cell transplantation (HSCT).
Overall, 56% of patients transitioned to HSCT, which was the most common reason for study discontinuation. In P2A, P1b, and P2B arms, transition rates were 69%, 38%, and 52%, respectively.
The toxicity profile was considered acceptable and as expected. Dr Lachowiez explained that infectious complications were most prevalent during cycle 1, while myelosuppression was prevalent during cycle 2. Overall, grades 3 and 4 adverse events occurring in 10% or more of patients included febrile neutropenia (50%), bacteremia (35%), and pneumonia (28%). The 30-day mortality rate was 0.0%. Deaths in patients while on study were due to sepsis, pneumonia, pulmonary hemorrhage, and the hemophagocytic syndrome.
Overall response for all patients was 82%: 97% in the newly diagnosed AML P2A arm, 72% in the R/R arms combined, and 75% and 70% in the R/R P1b and P2B arms, respectively. Event-free survival and overall survival (OS) were not reached in the newly diagnosed AML ND P2A arm and were 6 months (range, 3 to not evaluable) and 11 months (range, 2 to not evaluable) in the R/R P1b and P2B arms, respectively. One-year OS was 94%, 38%, and 68% for the newly diagnosed AML P2B, R/R P1b, and R/R P2A arms, respectively.
Dr Lachowiez described the regimen as an excellent bridge to HSCT in R/R AML, with 46% of these patients bridged to HSCT. One-year OS in patients with R/R AML was 87%, and the 1-year post-HSCT OS was 78%.
“In conclusion, we see that [venetoclax added to FLAG-IDA] is associated with expected and acceptable toxicity profiles,” said Dr Lachowiez,” [and] resulted in impressive efficacy in both newly diagnosed and relapsed/refractory AML.”
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
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- Lachowiez C, Konopleva M, Kadia TM, et al. Interim analysis of the phase 1b/2 study of the BCL-2 inhibitor venetoclax in combination with standard intensive AML induction/consolidation therapy with FLAG-IDA in patients with newly diagnosed or relapsed/refractory AML. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 332.
- Aboudalle I, Konopleva MY, Kadia TM, et al. A phase Ib/II study of the BCL-2 inhibitor venetoclax in combination with standard intensive AML induction/consolidation therapy with FLAG-IDA in patients with newly diagnosed or relapsed/refractory AML. Blood. 2019;134 (Supplement_1):176. doi:10.1182/blood-2019-121780
This article originally appeared on Hematology Advisor