The Importance of Real-World Data in Evaluating the Safety of Biosimilars: A Descriptive Study of Clinical Practice in an Oncohematological Italian Population

Abstract

The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs.

Keywords: biosimilars; chronic lymphocytic leukemia (CLL); non-Hodgkin lymphoma (NHL); oncohematology; rituximab; safety.

Figure 1

Blue: geographic distribution of participating hematology centers and patient enrollment in Italy (505 analyzed out of 800 enrolled). Black: participating hematology centers included in the study (number of naïve patients/number of enrolled patients); gray: participating hematology centers not included in the study (number of enrolled patients); n.: number.

Figure 2

Flowchart of the study: n.: number; ADR: adverse drug reaction; MabIV: Mabthera^® intravenous; MabSC: Mabthera^® subcutaneous; Rix: Rixathon^®; Tru: Truxima^®; IV: intravenous.

Figure 3

Sankey diagram of 505 naïve patients for the first eight infusions. For each patient, the description of the rituximab treatments at each infusion is graphically reported. MabIV: Mabthera^® intravenous; MabSC: Mabthera^® subcutaneous; Rix: Rixathon^®; Tru: Truxima^®; Disc: discontinuation.

Figure 4

Number of patients with at least one ADR related to RTX, by number of infusions and type of RTX (n = 85). MabIV: Mabthera^® intravenous; MabSC: Mabthera^® subcutaneous; Rix: Rixathon^®; Tru: Truxima^®.