PF525 SURVIVAL CONTINUES TO INCREASE IN DIFFUSE LARGE B‐CELL LYMPHOMA: A POPULATION‐BASED ANALYSIS AMONG 25,143 PATIENTS DIAGNOSED IN THE NETHERLANDS BETWEEN 1989 AND 2016
Authors: M. Durmaz, D.E. Issa, O. Visser, N.M. Blijlevens, S. Zweegman, M.J. Kersten, P.J. Lughtenburg, M.E. Chamuleau, A.G. Dinmohamed
Journal: HemaSphere (2019)

Background: The introduction of rituximab in the early 2000 s has revolutionized the management of diffuse large B‐cell lymphoma (DLBCL). Findings from our prior population‐based study in the Netherlands among DLBCL patients diagnosed up to 2010 showed an improvement in outcome since R‐CHOP was implemented in 2003 (Issa et al., Haematologica , 2015). Aims: Here, we extend our prior population‐based study with patients diagnosed up to 2016. This with the aim of assessing whether treatment practices changed and survival of DLBCL patients continues to increase in a contemporary era with well‐established therapy with R‐CHOP. Methods: We selected all adult (≥18 years) DLBCL patients diagnosed between 1989–2016 from the nationwide Netherlands Cancer Registry (NCR), with survival follow‐up up to January, 2018. Data on primary therapy—i.e. no therapy, radiotherapy (RT) alone, treatment with a chemotherapeutic (CT) backbone without RT and CT+RT,—were available in the NCR. Of note, information on rituximab use was only available in the NCR for patients diagnosed from 2007. We calculated relative survival rates (RSRs) and excess mortality ratios (EMRs) up to five years after diagnosis to estimate disease‐specific survival. All analyses were separately performed for patients with stage I (n = 6,534; median age, 68 years) and stages II‐IV DLBCL (n = 18,609; median age, 68 years), and stratified by time period (1989–2002, 2003–2010, and 2011–2016) and age (18–64, 65–74, and ≥75 years). The periods were selected based on the availability of rituximab in the Netherlands. Results: Treatment with RT alone decreased between 1989–2002 and 2003–2010 among patients with stage I DLBCL across all three age groups, following the wider application of CT+RT (Fig 1A). This trend was, less pronounced between 2003–2010 and 2011–2016 (Fig 1A). There were no major trends over time across the three age groups for the remaining treatment groups (Fig 1A). Most patients with stage II‐IV DLBCL, received CT without RT throughout the entire study period (Fig 1A). This was independent of age. Furthermore, there were no major discernible trends in primary therapy application between 2003–2010 and 2011–2016 across the three age groups for the remaining treatment groups (Fig 1A). During 2011–2016, ≥95% of the CT recipients in the three age groups across both stage groups received chemoimmunotherapy (CIT) with rituximab. The application of CIT remained steady during this period. Five‐year RSRs increased significantly over time among patients in the three age groups across both stage groups (Fig 1B‐C). However, the increase between 2003–2010 and 2011–2016 was less pronounced, as compared with the increase between 1989–2002 and 2003–20101/4 especially among patients with stage II‐IV DLBCL. After adjustment for age, sex, and year of follow‐up, patients with stage I and II‐IV DLBCL diagnosed in 2011–2016, as compared with 2003–2010, had 42% (EMR, 0.58; 95% confidence interval; 0.48–0.71; P &lt; 0.001) and 27% (EMR, 0.73; 95% confidence interval; 0.68–0.77; P &lt; 0.001) lower excess mortality, respectively. Summary/Conclusion: Collectively, in this nationwide population‐based study, we demonstrated that survival continues to increase among patients with DLBCL in contemporary clinical practice with well‐established first‐line therapy with R‐CHOP. This might be attributed to changes, albeit modest, in the application of primary therapy over time, along with advances in supportive care, staging techniques, and risk‐adapted therapy. The current study provides a benchmark to assess survival with novel treatment strategies for DLBCL. image