Importance of low- and moderate-grade adverse events in patients' treatment experience and treatment discontinuation: An analysis of the E1912 Trial

Although most trials typically focus on grade 3 or greater adverse events (AEs) when defining tolerability, authors of the E1912 trial, which examined use of ibrutinib-rituximab vs. FCR in the frontline setting for treatment of CLL, aimed to investigate whether lower grade AEs (grades 1 & 2) impacted drug tolerability and discontinuation. Perhaps not surprisingly, researchers found low- and moderate-grade AEs to be related to increased odds of increased patient side-effect bother and therapy discontinuation. Therefore, the authors argue that lower-grade AEs should be more emphasized in discussions of tolerability, particularly in phase 3 clinical trial data.