Time trends in primary therapy and relative survival of diffuse large B-cell lymphoma by stage: a nationwide, population-based study in the Netherlands, 1989-2018.

It is unclear whether survival in diffuse large B-cell lymphoma (DLBCL) continues to increase in an era where rituximab-containing chemotherapy reigns for almost two decades. Therefore, we evaluated trends in primary therapy and relative survival (RS) among Dutch DLBCL patients diagnosed between 1989 and 2018. Analyses were performed separately according to the stage I (N = 6952) and stage II-IV disease (N = 20,676), stratified by calendar period and age (18-64, 65-74, and ≥75 years). The use of chemotherapy ± radiotherapy increased over time across all age and stage groups. As of the mid-2000s, >95% of chemotherapy-treated patients received chemoimmunotherapy, irrespective of age and stage. Overall, RS increased significantly over time across all age groups, especially after 2003 when rituximab-containing chemotherapy had become the standard of care. However, RS increased less pronounced between 2003-2010 and 2011-2018 than between 1989-2002 and 2003-2010. These findings were congruent across all studied stage groups. Five-year RS across the three age groups during 2011-2018 was 96%, 84%, and 67% for stage I DLBCL and 75%, 60%, and 46% for stage II-IV DLBCL. Collectively, survival in DLBCL increased modestly beyond the initial introduction of rituximab, with apparent survival differences across age and stage that warrant novel treatment approaches.

Impact of rituximab biosimilars on overall survival in diffuse large B-cell lymphoma: a Dutch population-based study.

In 2017, the European Medicines Agency approved rituximab biosimilars (R-biosimilars) for treatment of diffuse large B-cell lymphoma (DLBCL). Thereafter, the Netherlands was one of the first countries to implement R-biosimilars, given lower costs compared with rituximab originator (R-originator). This study's objective was to investigate whether overall survival (OS) of patients with DLBCL receiving R-biosimilars is similar to patients treated with R-originator. DLBCL patients ≥18 years, diagnosed between 2014 and 2018, who received at least 1 cycle of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were identified in the Netherlands Cancer Registry. Patients were categorized into R-originator or R-biosimilars groups based on data from a central repository of the Dutch medicinal drug market. The primary end point was 3-year OS, defined as the time between diagnosis and all-cause death. By the end of 2018, 91% of purchased rituximab were biosimilars. In total, 4429 patients were identified with 876 in the R-biosimilars group and 3553 in the R-originator group. Patients in the R-biosimilars group less frequently received >6 cycles of R-CHOP compared with patients treated with R-originator (24% vs 30%, P = .003). The 3-year OS did not differ between patients treated with R-originator or R-biosimilars (73% vs 73%, P = .855). This was confirmed with a multivariable Cox regression analysis accounting for sex, age, International Prognostic Index score, and number of R-CHOP cycles. In conclusion, the 3-year OS is similar for patients treated with CHOP in combination with R-originator or R-biosimilars and, therefore, favors the use of R-biosimilars in DLBCL treatment management.