Bradley W. Christensen, MD, medical oncologist, Texas Oncology-Baylor Charles A. Sammons Cancer Center, discusses the process of patient selection for BCL-2 induction therapy in patients with acute myeloid leukemia (AML) in accordance with their individual disease characteristics.

Results from the phase 3 VIALE-A trial (NCT02993523) demonstrated that the combination of azacitidine plus venetoclax (Venclexta) improved patient responses compared with azacitidine alone in patients with AML who displayed high-risk features. The trial enrolled patients between 49 to 91 years of age, with a median age of 76 years, Christensen begins. All patients were characterized as intermediate or poor cytogenetic risk, and many had comorbidities that made them unfit for intensive induction therapy. According to mutation analysis, patients in the trial expressed 

Previous data have also indicated that patients age 60 or older experience increased rates of mortality with standard-of-care (SOC) 7+3 induction chemotherapy, Christensen adds. Based on these data, venetoclax and azacitidine treatment should be considered for patients older than 60 years with high-risk comorbid conditions, he states.

Patients who display complex karyotypes such as 

 mutations may also benefit from venetoclax and azacitidine approaches, as seen in the VIALE-A trial, Christensen continues. These patients experience greater toxicities, and do not typically respond favorably to SOC induction chemotherapy, Christensen explains. Although complete response rates with the BCL-2 inhibitor combination are not robust in younger patients within this subgroup, they are comparable to that of induction chemotherapy according to cross trial comparisons, Christensen reports. Moreover, the rate of toxicities is lower with BCL-2 inhibitors compared with induction chemotherapy in this population, he says. Intensive induction therapy is accordingly not recommended for patients expressing these mutations, regardless of if they also display lower-risk factors such as younger age, high fitness, drug-related AML, or secondary AML to myelodysplastic syndrome, Christensen states.

 mutations were shown to experience responses with venetoclax and azacitidine in this trial, Christensen says. However, these patients are also good candidates for intensive induction chemotherapy, he notes. Therefore, this result does not necessarily indicate that the BCL-2 inhibitor combination should be broadly adopted as the preferred option for these patients vs induction chemotherapy, Christensen concludes.

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Bradley W. Christensen, MD, discusses the process of patient selection for BCL-2 induction therapy in patients with acute myeloid leukemia in accordance with their individual disease characteristics.

Dr Christensen on the Influence of Patient Selection for BCL-2 Inhibitor Treatment 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.

Bradley W. Christensen, MD, discusses findings from the phase 3 VIALE-A trial in patients with acute myeloid leukemia. 

Bradley W. Christensen, MD

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Dr Christensen on the Influence of Patient Selection for BCL-2 Inhibitor Treatment in AML

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