Event-Free Survival at 24 Months Can Serve as Endpoint for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy
In a study reported in the Journal of Clinical Oncology, Maurer et al found that patients with diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy who achieve event-free survival at 24 months have overall survival that does not differ significantly from that in the general population. The findings suggest that event-free survival at 24 months can serve as an endpoint in clinical trials in newly diagnosed DLBCL.
Study Details
The study involved 767 patients (median age, 63 years; 53% male) with newly diagnosed DLBCL treated with immunochemotherapy who were prospectively enrolled in the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource and the North Central Cancer Treatment Group NCCTG-N0489 trial from 2002 to 2009. An external validation cohort included 820 patients (median age, 62 years; 55% male) from the Groupe d’Etude des Lymphomes de l’Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France.
Patient outcomes were evaluated at diagnosis and in the subsets of patients who were disease event-free at 12 and 24 months from diagnosis. Overall survival in the two cohorts was compared with age- and sex-matched general population for the United States and France. Observed vs expected overall survival was plotted using a conditional approach and summarized using standardized mortality ratios (SMRs) of observed to expected deaths.
U.S. Cohort Results
At a median follow-up of 60 months in the U.S. cohort, 12-month event-free survival was 77% and 24-month event-free survival was 71%. At diagnosis, patients had significantly decreased survival compared with the age-and sex-matched general population, with a standardized mortality ratio of 2.88 (P < .001).
Relative survival improved but was still significantly lower than in the general population among patients disease-free at 12 months (SMR = 1.40, P = .0038), but no significant difference in survival was observed between patients who were disease-free at 24 months and the general population (SMR = 1.18, P = .25).
French Cohort
At a median follow-up of 42 months in the French cohort, 12-month event-free survival was 80% and 24-month event-free survival was 73%. As in the U.S. cohort, patients had a significant survival deficit vs the general population at diagnosis (SMR = 4.99, P < .001), with survival improving among patients who were disease-free at 12 months (SMR = 2.06, P < .001) and not differing significantly from the general population among those disease-free at 24 months (SMR = 1.09, P = .71).
Simulation studies showed that 24-month event-free survival had comparable power compared with continuous event-free survival to detect differences in DLBCL relapse rates between treatment arms in clinical trials.
The investigators concluded, “[P]atients with newly diagnosed DLBCL who were treated with immunochemotherapy who are event-free 24 months after diagnosis have excellent outcome, with an [overall survival] equivalent to that of the age- and sex-matched general population in both US and French data sets. Consideration of [event-free survival at 24 months] as an end point in clinical trials and biologic studies of newly diagnosed DLBCL is warranted.”
Matthew J. Maurer, MS, of the Mayo Clinic, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported in part by the National Institutes of Health and the Henry J. Predolin Foundation. Study author Corrine Haioun, MD, reported a consultant or advisory role with Roche. Hervé Tilly, MD, receives research funding from Amgen.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
