Multicenter phase 2 trial of first-line acalabrutinib, venetoclax, and obinutuzumab in a CLL population enriched for high-risk disease

The AMPLIFY trial recently established fixed-duration acalabrutinib, venetoclax, and obinutuzumab (AVO) as a new standard of care first-line option for CLL with wildtype TP53. A multicenter phase 2 trial in the United States evaluated first-line AVO for a CLL population enriched for high-risk disease, defined by TP53 aberration. The study included 72 patients, among whom 45 patients with TP53 aberration. The complete response with undetectable MRD in bone marrow (BM-uMRD) rates at the start of cycle 16 were 42% in patients with TP53 aberration and 42% in all-comers; the BM-uMRD rates were 71% and 78%, respectively. Toxicities were mainly low-grade. After a median follow-up of 55,2 months, ten patients had progressed, including four with transformation, and three patients died. Four-year progression-free survival and overall survival were 70% and 96% for patients with TP53 aberration and 88% and 100% for patients without TP53 aberration, respectively. The authors conclude that first-line AVO was active and tolerated among patients with high-risk CLL.