D2.462 - Safety and predictors of tolerance in rituximab hypersensitivity management

Rituximab is one of the most widely used biologic agents across multiple immune-mediated and oncological conditions. Hypersensitivity reactions (HSRs) to rituximab constitute a major clinical challenge and frequently compromise treatment continuity. Structured diagnostic–therapeutic approaches, including drug provocation testing (DPT) and rapid desensitization, may enable safe re-exposure in selected patients. The aim of this study was to evaluate the safety of a standardized diagnostic–therapeutic protocol for rituximab HSRs and to explore potential predictors of tolerance to desensitization.

A retrospective observational study was conducted (June 2018 – May 2025) including patients with adverse reactions to rituximab who underwent DPT and/or rapid desensitization, following the diagnostic–therapeutic protocol previously described at Ramón y Cajal University Hospital (Madrigal-Burgaleta et al., 2019).

Demographic, clinical, laboratory, and allergy-related variables were collected. An exploratory predictive model of desensitization tolerance was built using penalized logistic regression with ElasticNet regularization, and performance was assessed through internal validation with 1,000 bootstrap resamples.

A total of 71 patients were included. Thirty-two DPTs were performed, with a tolerance rate of 72%. In 46 patients, 192 desensitizations were undertaken; 61.5% proceeded without reactions, and among those with reactions, 57% were successfully completed. Most reactions were mild to moderate, with no fatal or intractable events.

Although no predictor reached statistical significance, trends were observed for the severity of the initial reaction and the gradient between baseline and reaction tryptase. The predictive model achieved an apparent AUC of 0.85 (80% accuracy); after bootstrap correction, the adjusted AUC was 0.71 (95% CI: 0.59–0.84).

The diagnostic–therapeutic protocol for rituximab demonstrated safety and efficacy, achieving high desensitization completion rates and a low burden of clinically relevant reactions. The exploratory model for predicting desensitization tolerance showed moderate discriminative ability and limited accuracy, constrained by sample size. These findings underscore the need for larger, powered studies to validate predictive signals and improve individualized risk stratification.