Rituximab hypersensitivity reactions (HSR): Predictors of recurrent and severe reactions based on severity of reaction, NHL histologic subtype, and burden of disease.

Abstract

e18520 Background: Rituximab is an anti-CD20 monoclonal antibody with efficacy in B-cell malignancies. Grade II-IV HSR occur in 5-10% of patients. There are no data to predict which patients are at risk for more severe rituximab HSR as well as no data on eventual successful rituximab administration in this population. Methods: We analyzed all rituximab HSR in patients at Massachusetts General Hospital between 2006-2010. Patients included had documented HSR on the chemotherapy infusion sheet on our electronic medical record or via referral to allergy for desensitization. Control rituximab-treated patients were identified from tumor registry data. ICD3 codes were used to determine the histologic subtypes. Rates of HSR were analyzed by logistic regression and Fisher's exact test. Severity of HSR was based on an established classification system. Results: Immediate HSR occurred in 9% of patients (79/901) treated with rituximab and premedications. A majority of patients with a HSR developed symptoms on their initial infusion (76%); however, 46% of moderate or severe HSR occurred on subsequent infusions. Severity of HSR was directly correlated to the risk of a recurrent reaction where all patients with severe HSRs and 56% of patients with moderate HSRs had a recurrent reaction in contrast to only 36% of patients with mild reactions (p = 0.005). Advanced stage of disease increased the risk of a moderate or severe HSR (HR = 4, p = 0.02). Waldenstrom’s Macroglobulinemia (WM) accounted for 10% of all HSR while representing only 1% of rituximab treated pts (p < .003 adjusting for multiple comparisons) and 70% of these patients had a HSR. All patients with complex HSR who were referred to allergy for desensitization (n=14) were able to complete therapy safely. Conclusions: Severe rituximab HSR commonly occurs after the initial infusion. Severity of the HSR predicted recurrent HSR and an advanced stage of disease predicted more severe reactions. WM had a disproportionately higher risk for HSR. Despite HSR, we found that all patients were able to tolerate the recommended number of infusions without severe adverse events utilizing medical management and/or desensitization.