Early event status in Follicular lymphoma: providing simple endpoints for assessing outcomes in patients

The main purpose of the study was to demonstrate if early event free survival (EFS) could inform subsequent overall survival (OS) in newly diagnosed grade 1-3a Follicular Lymphoma (FL) patients (n=920) at 12 and 24 months from diagnosis (EFS12/EFS24). This article was written by Assistant Professor Matthew J. Maurer from the Mayo Clinic in Rochester, Minnesota, and his co-authors from various other centers; published in the American Journal of Hematology in July 2016.

The key findings of the article were:

• Patients who failed to achieve EFS12 were found to be associated with significantly increased mortality based on rates from the age and sex matched general population (MER SMR =3.72, 95% CI, 2.78-4.88, p<0.0001; Lyon SMR=8.74, 95% CI, 5.41-13.36, p<0.0001).
• Patients achieving EFS12 were reported to have excellent subsequent outcome, with no observed excess mortality beyond the age and sex matched general population (MER SMR=0.73, 95% CI, 0.56-0.94, p=0.016; Lyon SMR=1.02, 95% CI, 0.58-1.65, p=0.95).
• Patients failing to achieve EFS24 were associated with significantly increased mortality based on rates from the age and sex matched general population (MER SMR=13.02, 95% CI, 9.31-17.74, p<0.0001; Lyon SMR=7.22, 95% CI, 4.13-11.74, p<0.0001).
• Patients with early events after immunochemotherapy were reported to have poor outcomes (EFS12 failure: MER SMR=17.63, 95%CI:11.97-25.02, Lyon SMR=19.10, 95%CI:9.86-33.36; EFS24 failure: MER SMR=13.02, 95%CI:9.31-17.74, Lyon SMR=7.22, 95%CI:4.13-11.74).
• The observed mortality in patients with high (3-5) risk FLIPI at baseline who achieved EFS12 was not significantly greater than the age and sex matched general population (MER SMR=0.85, 95%CI, 0.53-1.28, p=0.50; Lyon SMR = 1.30, 95% CI,0.52-2.67, p=0.59).

Conclusions

This is the first comprehensive evaluation of relative survival from landmark time points of event status in a population of patients with FL diagnosed and managed in the rituximab/immunochemotherapy era. These results provide support for the re-assessment and updating of prognosis in FL patients at time points subsequent to diagnosis. Baseline FLIPI scores, which are powerful predictors of OS at diagnosis, no longer identify a subset of patients with increased mortality in the group of FL patients achieving EFS12. Patient status 12 months after diagnosis via EFS12 is a strong prognostic indicator in FL overall, although EFS24 should be considered in patients initially treated with immunochemotherapy. In this study, early event status as defined by EFS12 (non-aggressive therapy) and EFS24 (immunochemotherapy) provides a simple endpoint for outcomes in FL that do not require extended follow-up.

The article can be found here.

 Abstract

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here assessed if early events as defined by event-free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1-3a FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re-treatment, or death due to any cause. OS was compared to age-and-sex-matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR=3.72, 95%CI: 2.78-4.88; Lyon SMR=8.74, 95%CI: 5.41-13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR=0.73, 95%CI: 0.56-0.94, Lyon SMR=1.02, 95%CI: 0.58-1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR=17.63, 95%CI:11.97-25.02, Lyon SMR=19.10, 95%CI:9.86-33.36; EFS24 failure: MER SMR=13.02, 95%CI:9.31-17.74, Lyon SMR=7.22, 95%CI:4.13-11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL.