Multinational phase 3 trial of fixed-duration versus continuous treatment for chronic lymphocytic leukemia

Treatment of chronic lymphocytic leukemia (CLL) is either continuous therapy with Bruton’s tyrosine kinase (BTK) inhibitors or fixed-duration regimens combining venetoclax with either CD20 antibodies or BTK inhibitors. The multinational phase 3 CLL17 trial compared these approaches. The trial included 909 patients with previously untreated CLL. Patients were randomized to venetoclax-obinutuzumab (n=303), venetoclax-ibrutinib (n=305), or continuous ibrutinib monotherapy (n=301). The median duration of follow-up 34.2 months. Prespecified interim analysis found 3-year progression-free survival rate of 81.1% in the venetoclax-obinutuzunab group, 79.4% in the venetoclax-ibrutinib group, and 81.0% in the ibrutinib group. The results of each comparison met the criterion for noninferiority. Three-year overall survival rate was 91.5%, 96.0%, and 95.7%, respectively. The most common adverse events were infections, gastrointestinal disorders, and cytopenias. The authors conclude that in patients with previously untreated CLL, fixed-duration treatment with venetoclax-obinutuzumab or venetoclax-ibrutinib was noninferior to continuous ibrutinib with regard to investigator-assessed progression-free survival.