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ASH 2024 | Molecular predictors of response to venetoclax plus azacitidine in R/R AML
Jason Gilbert, MD, University of Colorado School of Medicine, Denver, CO, comments on the efficacy and molecular predictors of response for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) treated with venetoclax and azacitidine. Dr Gilbert highlights that the combination regimen of venetoclax and azacitidine is a promising option for patients in the R/R setting of AML, with favorable survival outcomes compared to traditional salvage regimens. Additionally, molecular data suggest that EZH2 mutations may be associated with worse outcomes, although further studies are needed to confirm this finding. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
Well, my project is looking at patients who are in the relapse or refractory setting of acute myeloid leukemia and an option for their treatment. So AML in general is a tricky cancer to treat, but it’s especially difficult when the cancer has relapsed or is refractory to initial therapy. And there’s been some strides made recently in frontline therapies, one being the combination regimen of the BCL2 inhibitor venetoclax with a hypomethylating agent such as azacitidine...
Well, my project is looking at patients who are in the relapse or refractory setting of acute myeloid leukemia and an option for their treatment. So AML in general is a tricky cancer to treat, but it’s especially difficult when the cancer has relapsed or is refractory to initial therapy. And there’s been some strides made recently in frontline therapies, one being the combination regimen of the BCL2 inhibitor venetoclax with a hypomethylating agent such as azacitidine. And it’s been proven very successful and helpful for patients who are not able to tolerate the more intensive chemotherapies in this setting. And so we retrospectively looked at this regimen for patients at our institution at University of Colorado who were in the relapse or refractory setting of AML. There were 46 patients that we had in our study and we found that the survival outcomes were pretty favorable compared to prior salvage regimens, typical salvage regimens with cytarabine-based chemotherapy. And we also saw that half of our patients were able to get a bone marrow transplant after the VEN-AZA regimen. We also looked at molecular data for these patients to see if there were any genes that might be associated with better or worse outcomes in this setting. And we found that the mutations in the gene EZH2, which encodes for a histone methylator, mutations in this gene are significantly associated with worse outcomes when treated in the setting with VEN-AZA. There are only five patients in our cohort who had this mutation so further analyses are needed to see if this signal is truly significant but it’s interesting to see that there was a mutation that correlates with worse outcomes. So in summary we found that VEN-AZA is an effective option for patients who have relapsed or refractory to therapy in AML, especially for patients who are able to get to the transplant setting. And we also found that EZH2 might portend worse outcomes, but further studies are needed to fully elucidate this.
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