Response rates in acute myeloid leukemia patients treated with attenuated durations of venetoclax in combination with hypomethylating agents.

Abstract

e19008 Background: The combination of the Bcl-2 inhibitor, venetoclax, with hypomethylating agents (HMA) recently emerged as an efficacious treatment for older adults with acute myeloid leukemia (AML) who are not eligible for intensive induction therapy. In a phase III randomized controlled trial of HMA +/- venetoclax, DiNardo et\xa0al demonstrated impressive composite complete response rate and complete response with incomplete recovery (CR+CRi) of 66% in the venetoclax arm as compared to 28% in the placebo arm. Despite HMA/Venetoclax being lower intensity, 83% of patients developed grade 3 hematologic adverse events, and 42% of patients experienced febrile neutropenia in the venetoclax arm, as compared to 19% in the placebo arm. In the trial, venetoclax was given continually for 28 day cycles, with some patients receiving shortened durations of venetoclax (21 days) due to toxicity. To reduce toxicity, some institutions have further limited the duration of venetoclax in cycle 1. Here, we report response rates with attenuated durations of venetoclax with HMA. Methods: We conducted a retrospective study of AML patients who received venetoclax in combination with HMA, excluding those with prior chemotherapy for AML or MDS, or previous exposure to HMA or venetoclax. Demographic, cytogenetic, pathology, and outcome data were collected including bone marrow biopsy results at diagnosis and after cycle 1 (day +28) or cycle 2 (day +56). The primary outcome was composite response rate (CR+CRi) following cycle 1 or cycle 2 defined by 2017 ELN criteria. Results: 25 patients were identified with median age of 73 (range 63-82). 9 patients received 14 or less days of venetoclax (attenuated duration): < 8 days in 1 patient and 8-14 days in 8 patients. 16 patients received 21 days or more (standard duration): 21 days in 14 patients, and 28 days in 2 patients. Of the patients who received an attenuated duration, the median age was 74 (68-82), 22% had either a TP53 mutation or deletion, 56% had complex karyotype, and 44% had received prior cytotoxic chemotherapy. Of the patients who received standard duration therapy, the median age was 71 (63-81), 44% had either a TP53 mutation or deletion, 75% had complex karyotype, and 6% had received prior cytotoxic chemotherapy. The composite response rate was 78% in the attenuated duration group and 75% in the standard duration group (p > 0.99). Conclusions: Though a limited sample size, this data suggests high response rates can be observed with attenuated courses of venetoclax. With appropriately selected patients, the feasibility of attenuated venetoclax courses could be further explored in larger prospective studies.[Table: see text]