Multinational phase 3 trial of first-line acalabruinib combinations in chronic lymphocytic leukemia

It is unknown whether fixed-duration acalabrutinib-venetoclax, with or without obinutuzumab, would result is better progression-free survival than chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL). The phase 3 AMPLIFY trial, at 133 centers across 27 countries, randomized patients 1:1:1 to 14 cycles of acalabrutinib-venetoclax, 14 cycles of acalabrutinib-venetoclax-obinutuzumab, or investigator’s choice of chemoimmunotherapy. The median duration of follow-up was 40.8 months. Three-years PFS was 76.5% with acalabrutinib-venetoclax versus 66.5% with chemoimmunotherapy (p=0.004) and 83.1% with acalabrutinib-venetoclax-obinutuzumab versus 66.5% with chemoimmunotherapy (p<0.001). Three-year overall survival was 94.1% with acalabrutinib-venetoclax, 87.7% with acalabrutinib-venetoclax-obinutuzumab, and 85.9% with chemoimmunotherapy. Neutropenia, the most common adverse event of clinical interest of grade 3 or higher, was reported in 32.3%, 46.1%, and 43.3% in the three groups, respectively. The authors conclude that acalabrutinib-venetoclax, with or without obinutuzumab, significantly prolongd PFS as compared with chemoimmunotherapy in patients with previously untreated CLL.