The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

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.


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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.

Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.

References

  1. 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.
  2. 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