Oncology TA Head and Sr. Director, Global Epidemiology AbbVie chapel hill, United States
Background: Combination therapy with Venetoclax + hypomethylating agents (VEN-HMA) has become the standard of care for newly diagnosed (ND) acute myeloid leukemia (AML) patients (pts) ineligible for intensive chemotherapy.
Objectives: To examine management and outcomes of ND AML pts initiating VEN-HMA in US community practice in the first 3 years after FDA approval for this indication.
Methods: Retrospective cohort study of ND adult AML pts initiating VEN in community practice from the ConcertAI Oncology Dataset w/in 60 days of diagnosis between 12/1/18 to 10/31/21 in combination with an HMA (azacytidine or decitabine) as the first line (1L) therapy. VEN dosage, dose modifications, composite complete remission (CRc) rate, and timing of bone marrow biopsies (BM Bx) were curated from unstructured EMR data. Blast clearance was defined as BM blasts < 5%. Pts were followed from VEN start (index date) to end of record, end of study on 2/28/22, or death. K-M methods evaluated time to CRc and overall survival (OS).
Results: A total of 250 pts met inclusion criteria, with further restriction to pts who initiated HMA ±3 days of index (N=196) at cycle 1. Mean age was 77 years, 46% had 2ndary AML, and 23% had ECOG score ≥2. 68% of pts had VEN dose ramp up (RU). Median duration of RU was 3 days with most pts increasing from 100 mg (87%) to 400 mg (77%). Overall, 31% (n=60) of pts had strong/moderate CYP3A4 inhibitors (CYP3A4i) at index. RU starting and ending doses for pts with CYP3A4i (n=39) were lower relative to those without, per label recommendation. Median (IQR) duration of follow-up and VEN-HMA duration was 8.6 (10.4) and 4.1 (6.3) months, respectively. Median cycles of VEN-HMA was 3 and median VEN days dosed per cycle was 24 (IQR 11). 61% of pts had a BM Bx during 1L therapy (among those, median of 48 days from index date), 33% within ±14 days of day 28. 39% of pts discontinued VEN(among those, 36% due to disease progression). Overall, 79% had a VEN dose interruption, 30% had ose decrease at any time during 1L, and 17% had a decrease in VEN days dosed per cycle, with modifications commonly due to cytopenia. Within 60 days of index, 13.3% of pts died. CRc was achieved in 54.1% of pts within median of 4.2 (95% CI 3.1-6.5) months. Median OS was 10.1 (95% CI 8.6-12.2) months.
Conclusions: This study of early post-approval experience of VEN-HMA for ND AML pts indicates that a majority received recommended dosage, RU, and VEN modification with concomitant CYP3A4i. However, timing of early response evaluation by BM Bx was suboptimal and highlights the need for continued focus to optimize outcomes. VEN dose modification to manage cytopenia was common, and number of days dosed per cycle remained in line with label recommendation. Median OS and CRc were similar to other recent studies of AML pts treated with VEN-HMA in US. community practices.
