Azacitidine Plus Venetoclax for the Treatment of Relapsed and Newly Diagnosed Acute Myeloid Leukemia Patients

Abstract

Venetoclax (VEN) belongs the BH3-mimetic class that selectively targets BCL-2, activating apoptosis. The combination of VEN and azacitidine (AZA) has changed the paradigm of treatment of newly diagnosed (ND) acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. There is scarce evidence for the use of VEN–AZA for relapsed or refractory (R/R) AML. We compared the outcome of 39 R/R AML and 38 ND AML patients treated between 01/20 and 12/21. The median age was 69 (22–86) and 73 (61–81) in the R/R and ND groups, respectively. Adverse cytogenetics were found in 36% of patients in the R/R group and 59% of patients in the ND group. Overall response rate was 37% in R/R AML, including 13% CR, 8% CRi, 3% PR and 13% MLFS, and 58% in the ND AML, including 32% CR, 13% CRi and 13% MLFS. Adverse cytogenetics was associated with treatment failure in the R/R group (Relative Risk = 0.13, p = 0.005). Median overall survival (OS) was 5.9 months in the R/R group and 9.4 months in the ND group. Median OS was 2.2 months in the adverse cytogenetics group versus 8.7 months in the intermediate cytogenetics group in the R/R group (p = 0.02). Median leukemia-free survival was not different between the two groups (9.4 months and 10.3 months), indicating that VEN–AZA can be an efficient salvage treatment for selected R/R AML patients. In conclusion, VEN–AZA is a promising treatment for ND AML and for selected R/R AML patients.

Molecular predictors of response to venetoclax plus hypomethylating agent in treatment-naïve acute myeloid leukemia

“…It is to be noted that OS in our cohort was inferior compared with the VIALE-A study 1 but akin to a real world analyses of newly diagnosed AML patients treated with Ven+ azacitidine due to enrichment with secondary AML. 1 , 12 Taken together, our findings which require further validation suggest an independent prognostic impact of ASXL1 mutation in treatment-naïve AML patients receiving Ven+HMA.…”

Conventional Therapeutics in BPDCN Patients—Do They Still Have a Place in the Era of Targeted Therapies?

“…However, relapses occur often, and studies have been implemented to evaluate them in combination with other agents. One of the most studied combinations is with 5-azacytidine, already approved (since 2018) for treating newly diagnosed AML for patients >75 years old or with comorbidities and ineligible for intensive induction chemotherapy [ 22 , 23 , 24 , 25 , 26 ]. Thus, a combination of hypomethylating agents is currently under investigation in two different clinical trials against BPDCN (NCT03113643 and NCT03404193).…”

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

“…Although the approval for use is currently confined to patients with ND-AML, mounting evidence indicates increasing off-label use of these combinations to treat refractory/relapsed (R/R) AML because of their efficacy and safety profile. According to a series of reports [ 7 , 8 , 9 , 10 ], VEN-HMA combinations have yielded response rates as high as 64% in R/R-AML patients [ 8 ], which appears to be noninferior to results with salvage IC [ 10 ], even though the treatment intensity of the VEN combination is much lower than that of conventional cytotoxic salvage regimens.…”

“…Indeed, several reports describe the successful use of this regimen as a bridge to potentially curative allo-HCT in elderly patients with ND-AML or R/R-AML [ 4 , 7 , 10 , 13 , 14 , 15 , 16 , 17 ]; however, data about clinical outcomes after allo-HCT are still lacking. In this study, we evaluated the post-transplant outcomes of patients who received VEN-HMA as initial therapy for ND-AML or as a salvage regimen for R/R-AML.…”