A clinical prediction model for infusion-related reactions to rituximab in patients with B cell lymphomas

Abstract

Background Infusion-related reactions (IRRs) are a major adverse event of rituximab. Objective To develop a prediction model for IRRs to rituximab among patients with B cell non- Hodgkin's lymphomas (B-NHL). Setting A 1000-bed university hospital in Tokyo. Methods Patients with B-NHL treated with rituximab at our institution from 2004 to 2014 were retrospectively analysed. Chills, fever, rash, nausea, asthenia, headache, cardiovascular symptoms, and respiratory symptoms of any grade, in association with rituximab infusion, were identified as IRRs. Risk factors for IRRs to rituximab found in the intergroup analysis were subsequently evaluated by using multivariate analysis. Main outcome measure Occurrence of IRRs to rituximab. Results A total of 140 patients with various types of B-NHL, including 74% with diffuse large Bcell lymphoma, were analysed. Among them, 55 and 85 patients were assigned to the IRR group and the non-IRR group, respectively. Indolent histological subtypes, bulky disease (>10 cm), B symptoms, higher serum soluble interleukin-2 receptor concentration, and bone marrow involvement were more common in the IRR group. The multivariate logistic regression analysis identified low-grade lymphomas [odds ratio (OR) 2.81, p = 0.017] and bulky disease (OR 2.52, p = 0.037) as independent risk factors for IRRs to rituximab. The incidence rates of IRRs to rituximab among patients with neither, one, or both of these risk factors were 26, 54, and 78%, respectively (χ = 16.4, p < 0.001). Conclusions A simple combination of histopathological subtype and bulkiness of disease could predict the risk of IRRs to rituximab among patients with B-NHL.

Factors Influencing Infusion-Related Reactions Following Dosing of Reference Rituximab and PF-05280586, a Rituximab Biosimilar

“…Previously, Paul and Cartron [26] reported lymphocyte count, bulky disease, low-grade B-cell NHL, the level of CD20 expression on CLL cells, and Fc/Fc gamma receptor (FcγR)-mediated interactions between natural killer (NK) cells and CD20+ cells as being associated with the occurrence of IRRs. In the observational setting in patients with hematologic malignancies, predictive indicators of rituximab IRRs have included bone marrow involvement, body weight, low-grade lymphomas, and bulky disease [27][28][29].…”

A novel rituximab administration protocol to minimize infusion-related adverse reactions in patients with B-cell non-Hodgkin lymphoma

“…The secondary outcomes were the overall incidence of IRRs to the rst and second cycles of rituximab, the infusion rates of rituximab during the onset of an IRR, the conversion rate to short infusion at the third cycle in each group, and the overall conversion rate to short infusion at the third cycle. We set the target number of patients as 70 to validate IRR incidence in each risk group; this was half the number selected for our previous study, in which approximately 40% of the patients experienced IRRs to rituximab [7]. The sample size was equivalent to the minimum required to detect a 30% reduction in IRR incidence in all patients with 80% power and 10% alpha error based on a one-sided test.…”

“…In a previous study, we demonstrated that low-grade histology and bulky disease with a tumor diameter > 10 cm are independent risk factors for IRRs to rituximab [7]. However, to the best of our knowledge, no prospective or retrospective studies have evaluated a novel protocol that can minimize IRRs to rituximab among B-NHL patients with various risk factors.…”

“…We strati ed patients into low-, moderate-, and high-risk groups according to the observed number of risk factors (0, 1, and 2 risk factors, respectively) identi ed in our previous study, speci cally, an indolent histology and the presence of a bulky disease with a tumor diameter > 10 cm [7]. Following this strati cation, we established a rituximab dosing regimen for the rst and second cycles.…”

“…Following this strati cation, we established a rituximab dosing regimen for the rst and second cycles. The infusion procedure in the third cycle was at the attending physician's discretion since most IRRs occur during the initial rituximab administration and the incidence of IRRs is known to decrease in subsequent cycles [7,8].…”