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

Abstract

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.

Fig. 1. Primary treatment of adult patients diagnosed with stage I DLBCL in the Netherlands.

A shows the results of primary therapy in broad categories according to age at diagnosis and calendar period of diagnosis for patients diagnosed during the calendar period 1989–2018. B shows the specific type of primary therapy according to age at diagnosis and calendar year of diagnosis for patients diagnosed between 2014 and 2018. The proportion of patients receiving a particular treatment within a specific calendar period or year and age group are presented in the column below. CT chemotherapy, CMT combined modality treatment, RT radiotherapy, R rituximab, CHOP cyclophosphamide, doxorubicin, vincristine, and prednisone.

Fig. 2. Primary treatment of adult patients diagnosed with stage II–IV DLBCL in the Netherlands.

A shows the results of primary therapy in broad categories according to age at diagnosis and calendar period of diagnosis for patients diagnosed during the calendar period 1989–2018. B shows the specific type of primary therapy according to age at diagnosis and calendar year of diagnosis for patients diagnosed between 2014 and 2018. The proportion of patients receiving a particular treatment within a specific calendar period or year and age group are presented in the column below. CT chemotherapy, CMT combined modality treatment, RT radiotherapy, R rituximab, CHOP cyclophosphamide, doxorubicin, vincristine, and prednisone.

Fig. 3. Relative survival of adult patients diagnosed with DLBCL in the Netherlands according to age at diagnosis and calendar period of diagnosis.

Relative survival of patients with stage I disease is presented according to the following age categories: A 18–64, B 65–74, and C ≥ 75 years. The corresponding relative survival of patients with stage II–IV disease is shown in panels D to F. Lastly, relative survival for all stages combined is displayed in panels G to I. The table presents the projected 5- and 10-year relative survival rates with 95% confidence intervals according to age at diagnosis and calendar period of diagnosis. The asterisk indicates the P value for the likelihood ratio test assessing linear trends in relative survival over the calendar periods studied.