Adverse event reporting patterns of rituximab and obinutuzumab in B-cell non-Hodgkin lymphoma: a FAERS...

Rituximab and obinutuzumab share the CD20 target but are used across distinct B-cell non-Hodgkin lymphoma (B-NHL) subtypes, treatment backbones, and clinical eras. Their real-world adverse event (AE) reporting patterns remain incompletely characterized.

To characterize AE reporting patterns for rituximab and obinutuzumab in B-NHL using FAERS, evaluate signal retention across histological subtype and calendar-period strata and after COVID-associated report exclusion, and describe serious outcome reporting patterns during the common-market period.

FAERS reports listing rituximab or obinutuzumab as the primary suspect drug with B-NHL indications from January 2004 to December 2024 were extracted. Disproportionality signals were evaluated using reporting odds ratios (RORs) and Bayesian Confidence Propagation Neural Network (BCPNN)-derived information components (ICs). Pooled B-NHL analyses identified candidate System Organ Class (SOC)- and Preferred Term (PT)-level reporting signals. Candidate signals were further evaluated across histological subtype and calendar-period strata and in a sensitivity analysis excluding reports containing COVID-associated PTs. Multivariable logistic regression assessed serious outcome reporting during the common-market period.

In pooled B-NHL analyses, both drugs showed overlapping SOC-level reporting domains, including hematologic, infection-related, respiratory, vascular, and hepatobiliary disorders. Infusion related reaction was the most uniformly retained PT-level signal for both drugs, whereas cytopenia-related hematologic signals showed broad but non-uniform retention. Infection-related, respiratory, and neoplasm-related findings required contextual interpretation according to reporting era, histological subtype, component PT heterogeneity, or survivorship background. Most pooled candidate clinical PT-level signals remained signal-positive after exclusion of COVID-associated reports. Obinutuzumab reports had higher adjusted odds of serious outcome reporting during 2014-2019 (aOR 1.59, 95% CI 1.42-1.77) but not during 2020-2024 (aOR 1.03, 95% CI 0.94-1.12), with a significant drug-by-period interaction.

FAERS reports involving rituximab and obinutuzumab in B-NHL showed overlapping AE reporting domains, but pooled signals differed in retention across clinical and reporting contexts. Infusion related reaction was the clearest consistently retained PT-level finding, whereas cytopenia-related hematologic events formed a broad but non-uniform reporting domain. Signal-retention analyses may help prioritize pharmacovigilance hypotheses and setting-specific AE monitoring, but these reporting patterns require validation in longitudinal data sources and should not be interpreted as causal or direct comparative safety estimates.