Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy

Abstract

Purpose: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data.

Patients and methods: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France.

Results: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL.

Conclusion: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Event description in the US cohort at diagnosis, in patients achieving event-free survival at 12 or 24 months. (A) Assessment at diagnosis; (B) event free 12 months since diagnosis; (C) event free 24 months since diagnosis. DLBCL, diffuse large B-cell lymphoma; MDS, myelodysplastic syndrome.

Fig 2.

Overall survival versus expected survival in US cohort at diagnosis, in patients achieving event-free survival at 12 (EFS12) or 24 (EFS24) months. (A) Overall survival since diagnosis; (B) overall survival since EFS12 evaluation; (C) overall survival since EFS24 evaluation. DLBCL, diffuse large B-cell lymphoma.

Fig 3.

Cause of death in the US cohort at diagnosis, in patients achieving event-free survival at 12 or 24 months. (A) Assessment at diagnosis; (B) event free 12 months since diagnosis; (C) event free 24 months since diagnosis. DLBCL, diffuse large B-cell lymphoma; MDS, myelodysplastic syndrome.

Fig 4.

Overall survival versus expected survival in French cohort at diagnosis, in patients achieving event-free survival at 12 (EFS12) or 24 (EFS24) months. (A) Overall survival since diagnosis; (B) overall survival since EFS12 evaluation; (C) overall survival since EFS24 evaluation. DLBCL, diffuse large B-cell lymphoma.

Fig 5.

Forest plots of standardized mortality ratio in combined data set by diffuse large B-cell lymphoma subgroups at diagnosis, in patients achieving event-free survival at 12 (EFS12) or 24 (EFS24) months. (A) All patients since diagnosis; (B) EFS12 patients from 12 months since diagnosis; (C) EFS24 patients from 24 months since diagnosis. IPI, International Prognosis Index; LDH, lactate dehydrogenase; PS, performance status.