Early event status informs subsequent outcome in newly diagnosed follicular lymphoma

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.

How I manage patients with follicular lymphoma

“…Our analysis of the National LymphoCare Study identified the poor prognostic impact of POD24, with 50% OS at 5 years, compared to 90% in patients without early progression (Casulo et al , ). These findings have had high reproducibility and validity in a number of studies and, as such, POD24 is considered among the most robust markers of poor outcome in FL (Jurinovic et al , ; Maurer et al , ). Earlier time points of progression have also been evaluated by Maurer and colleagues.…”

Can histologic transformation of follicular lymphoma be predicted and prevented?

“…Early progression, most commonly defined as progression within 2 years after starting rituximabchemotherapy, occurs in ;20% of patients and has recently been associated with poor outcome. [6][7][8][9] Similarly, transformation to aggressive lymphoma, occurring in 2% to 3% of patients per year, has repeatedly been linked to adverse prognosis when compared with patients not experiencing transformation. [10][11][12][13][14][15] There is an association between early progression and transformation.…”

The case for lymphoma-specific survival

“…Although it is unclear whether there is a late plateau in the HT curves [9]; HT is more frequent [7,8] and aggressive [10,11] shortly after diagnosis. Conversely, patients with remission persisting 2 years after diagnosis (or perhaps as early as 1 year) can expect to live as long as the general population [12], which seems to indicate that their risk of death from either the disease or toxicity is lower. In a recent study analyzing the outcome of FL patients based on their response to front-line ICT [7], we found that most patients with ICT-refractory disease were dead at the time of analysis (31/53, 58%), mostly due to lymphoma (27/31, 87%) while only a minority of ICT-sensitive patients had died (35/290, 12%), 14 (40%) due to lymphoma and 10 (29%) due to toxicity (unpublished data).…”