Susan O’Brien, MD, of the University of California, Irvine, CA, provides an insightful look into the Phase III ALLIANCE A041202 trial (NCT01886872), which by having three arms: bendamustine plus rituximab, ibrutinib, and ibrutinib plus rituximab, aimed to establish the most effective initial therapy for elderly patients with chronic lymphocytic leukemia (CLL). Prof. O’Brien speaks from the American Society of Hematology (ASH) 2018 Annual Meeting and Exposition in San Diego, CA, and highlights the superiority, in terms of PFS, of the ibrutinib monotherapy arm, before revealing why this study has practice-changing implications.