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 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 IDH1/2 (25%), TP53 (23%), NPM1 (17%), and FLT3 (14%) mutations.

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 TP53 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.

Lastly, patients with IDH1/2 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.