impact of rituximab biosimilars on overall survival among PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA IN THE NETHERLANDS; a nationwide, population-based cohort study
In 2017, rituximab biosimilars (R-biosimilars) for treatment of diffuse large B-cell lymphoma (DLBCL) was approved. Until now, safety regarding treatment-related toxicities of R-biosimilars was evaluated in prospective studies on rheumatoid arthritis and naïve follicular lymphoma. However, patient numbers were limited in order to assess non-inferiority in efficacy of R-biosimilar¾in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)¾of patients with DLBCL. Therefore, this population-based study aimed to assess the 2-year overall survival (OS) of patients with DLBCL treated with R-biosimilars or rituximab originator (R-originator) in the Netherlands.
All DLBCL patients ≥18 years diagnosed between 2014-2018 with at least one cycle of R-CHOP were identified in the Netherlands Cancer Registry. Detailed information on baseline characteristics, diagnostics and first-line therapy was available for all patients. Patients were categorized into R-originator and R-biosimilars groups using data from a central repository of the Dutch medicinal drug market. The primary endpoint was 2-year OS, defined as the date from DLBCL diagnosis to all-cause death. Patients alive were censored at February 1, 2020. Multivariable evaluation was performed using Cox regression. P<0.05 indicates statistical significance. Due to time dependency, differences in follow-up time between R-originator and R-biosimilars was unavoidable. Therefore, a sensitivity analysis was performed by excluding all patients in the R-originator group diagnosed in the pre-EMA approval period of R-biosimilars.
By the end of 2018, 91% of purchased rituximab by the Dutch hospitals were biosimilars. In total, 4,430 patients with DLBCL who received at least one cycle of R-CHOP were identified. Of these patients, 876 (20%) were categorized in the R-biosimilars group and 3,554 (80%) in the R-originator group. Sex and age distribution was similar between the two subgroups. Patients in the R-biosimilars group less frequently received >6 cycles of R-CHOP as compared to patients treated with R-originator (24% vs. 30%, P=0·003). The 2-year OS did not differ between patients treated with R-originator or R-biosimilars (77% vs. 78%, P=0·775). Risk of survival between R-originator and R-biosimilars remained similar after adjustment for sex, age, International Prognostic Index (IPI) score and number of R-CHOP cycles. In the sensitivity analysis, the frequency of >6 cycles of R-CHOP as well as the 2-year OS was similar for patients treated with R-originator or with R-biosimilars.
The results in this independent validation 'real world' population study confirm equivalent efficacy in patients with DLBCL treated with either R-originator or R-biosimilars¾in combination with CHOP¾resulting in a significant reduction of costs in the Dutch healthcare system. Thus, our conclusion has far-reaching consequences at the level of global implementation of rituximab biosimilars, and consequently, containment of global health care expenditure in treatment of hematological malignancies.