# Investigating rituximab-induced infusion-related reactions in patients with non-Hodgkin lymphoma, with a focus on follicular lymphoma: a retrospective observational study

## TL;DR

This study found that patients with follicular lymphoma experience higher rates of rituximab infusion-related reactions, which can be predicted by blood tests.

## Contribution

The study identifies lymphocyte counts and specific cytokine levels as predictors of infusion-related reactions in follicular lymphoma patients.

## Key findings

- IRRs occurred in 59.0% of follicular lymphoma patients compared to 40.3% in diffuse large B-cell lymphoma patients.
- Lymphocyte counts ≥ 1,600/µL were strongly associated with IRRs in follicular lymphoma patients.
- Interferon-γ, chemokine ligand 26, and vascular endothelial growth factor levels were linked to IRRs in follicular lymphoma.

## Abstract

The incidence of infusion-related reactions (IRRs) caused by rituximab is very high, and many studies have explored factors related to the onset of IRR; however, most analyses have been conducted on a mixed range of disease indications. This study aimed to investigate rituximab-induced IRR in patients with non-Hodgkin lymphoma (NHL), particularly follicular lymphoma (FL), and examine the factors related to its occurrence.

Data on sociodemographic and blood test findings were collected on the closest possible date prior to rituximab administration. Cytokine/chemokine levels in the blood samples were measured before the drug administration. During rituximab administration, vital signs, including pulse, oxygen saturation, respiratory rate, and body temperature, were carefully monitored. IRRs were defined as adverse reactions that occurred within 24 hours of drug administration, the grades of which were assessed using the Common Terminology Criteria for Adverse Events, version 5.0.

IRRs were reported in 119/252 NHL cases (47.2%), with incidences of 36/61 (59.0%) FL cases and 48/119 (40.3%) diffuse large B-cell lymphoma (DLBCL) cases; the incidence of IRR was significantly higher in FL (p = 0.0174). Logistic regression analysis in FL revealed a significant correlation between IRR expression and lymphocyte counts of ≥ 1,600/µL (odds ratio 14.0, p = 0.0162). Additionally, interferon-γ (p = 0.0262), chemokine ligand 26 (p = 0.0394), and vascular endothelial growth factor (p = 0.0359) levels in FL.

The incidence of IRR differed significantly between patients with FL and those with DLBCL. In FL, rituximab is administered while monitoring the disease condition and when the tumor burden is relatively large, which is thought to increase the frequency of IRR, suggesting that lymphocyte count can lead to effective prediction. The occurrence of IRR can be predicted by measuring the blood cytokine and chemokine levels before rituximab treatment, leading to the provision of safe and useful treatment.

The online version contains supplementary material available at 10.1186/s40780-026-00538-6.