Importance of low- and moderate-grade adverse events in patients’ treatment experience and treatment discontinuation

Mild (grade 1) and moderate (grade 2) adverse events (AEs) are often not reported in phase 3 trials. Analysis of patients in the E1912 trial (ibrutinib versus chemoimmunotherapy for CLL) found that both the odds of increased self-reported side-effect bother and the odds of imminent treatment discontinuation because of side effects increased with the count of low- and moderate-grade AEs within a patient treatment cycle. These increased odds were greater for AEs defined as symptomatic on the basis of criteria defined for patient self-reporting of AEs. The authors conclude that limiting AE reporting to grade 3+results could lead to missing important contributors to treatment side-effect bother and discontinuation.