Dr Christensen on Azacitidine Plus Venetoclax in AML

Bradley W. Christensen, MD, medical oncologist, Texas Oncology-Baylor Charles A. Sammons Cancer Center, discusses findings from the phase 3 VIALE-A trial (NCT02993523) in patients with acute myeloid leukemia (AML).

VIALE-A randomized 433 patients 2:1 to receive either azacitidine (Vidaza) plus venetoclax (Venclexta) or azacitidine alone and demonstrated improved response rates in the high-risk patients who received the combination, Christensen says. This trial enrolled patients with a median age of 76 years. In the azacitidine/venetoclax and azacitidine alone arms, 25% and 24% of patients had secondary AML, respectively. Additionally, 36% and 39% of the combination and control arms had poor cytogenetic risk, respectively, and 49% and 45% had at least 2 contraindications to intensive therapies, respectively.

Overall survival (OS) is an important end point to reach in clinical trials, especially for patients with a disease as deadly as AML, Christensen notes. In VIALE-A, the median OS with azacitidine/venetoclax was 14.7 months vs 9.6 months with azacitidine alone. Additionally, the complete response (CR) rate was 36.7% with the combination vs 17.9% with azacitidine alone, and the composite CR rates were 66.4% and 28.3%, respectively. In the azacitidine/venetoclax arm, the median time to CR was 1.3 months, vs 2.8 months with azacitidine alone, indicating that of the patients who were going to achieve a CR from the combination, most did so after 1 treatment cycle.

Azacitidine plus venetoclax was also a relatively well-tolerated regimen in this high-risk patient population, especially when compared with the safety profile of 7+3 chemotherapy, which was not administered in VIALE-A but which is a standard of care (SOC) in AML, Christensen explains. Common adverse effects with 7+3, including cardiac toxicities and mucositis, did not occur in VIALE-A. However, many patients who received the azacitidine/venetoclax combination did experience myelosuppression, which should be managed appropriately, Christensen says.

Overall, the findings from VIALE-A demonstrate that azacitidine plus venetoclax should be considered the new SOC in elderly patients with AML or those with comorbidities who are unfit for intensive induction therapy, Christensen concludes.