Venetoclax with 5+2 chemo looks effective in older AML patients

There was one dose-limiting toxicity in a patient in cohort E (600 mg venetoclax). There were three deaths, all from sepsis, during the induction period (within 42 days) and one after 42 days. The deaths occurred in cohorts C, D, and E.

At the time of data cutoff, two patients had completed treatment, six were continuing, and 33 had discontinued. The primary reason for discontinuation was disease relapse, followed by refractory disease, adverse events, dose-limiting toxicity, or physician/patient decision.

Other adverse events included infections, including grade 3 infections in all 16 patients treated at the 400 mg and 600 mg levels, as well as sepsis, febrile neutropenia, and grade 3 rapid atrial fibrillation in two patients treated in the 400 mg and 600 mg venetoclax cohorts.“Overall, the impression from the investigators was that this is a very deliverable and well-tolerated regimen,” Dr. Wei said.

The overall combined CR/CRi rate was 71%, including CR/CRi in all 9 patients in the 200 mg venetoclax dose cohort.

“Even just with 1 week of monotherapy venetoclax exposure, 25% of patients had a 50% reduction in their bone marrow blasts,” Dr. Wei said.

Median overall survival among the 37 evaluable patients was 7.7 months. Among 12 patients who achieved a CR, the median overall survival was 18.5 months, and among the 12 patients with a CRi, the median overall survival was 7.7 months. For the remaining 13 patients, the median overall survival was 6.3 months.

Survival was significantly better for patients who were treatment-naive prior to venetoclax and chemotherapy, at a median of 18.6 months, compared with 3.8 months for patients who had previously received a hypomethylating agent and/or low-dose cytarabine (P = .0018).

Dose expansion of the 600-mg cohort is ongoing to provide better perspectives on efficacy.

The findings provide evidence that venetoclax monotherapy has cytoreductive potential and support future exploration of venetoclax in combination with 7+3 chemotherapy in younger, fit adults with AML, Dr. Wei said.

The study was supported by AbbVie/Genentech, the Victorian Cancer Agency, and the National Health and Medical Research Council of Australia. Dr. Wei reported research support and advisory board activities with AbbVie and other companies.

SOURCE: Wei AH et al. EHA Congress, Abstract S1564.