The Importance of Age in Prognosis of Follicular Lymphoma: Clinical Features and Life Expectancy of Patients Younger Than 40 Years
Authors: Lobetti-Bodoni Chiara , Rancoita Paola MV , Montoto Silvia , Lopez-Guillermo Armando , Conconi Annarita , Coutinho Rita , Matthews Janet , Franceschetti Silvia , Bertoni Francesco , Cavalli Franco , Ghielmini Michele , Lister Andrew , Montserrat Emili , Zucca Emanuele 
Published: October 2019

Abstract
Abstract 1593

Background
The median age at presentation of follicular lymphoma (FL) is around 60 years (yrs). Despite recent reports of general improvement of overall survival (OS) in the last decade, the outcome of younger patients (pts) with FL has not been extensively investigated.

Patients and methods
Our study aimed to investigate possible differences in clinical features, therapy and outcome in FL pts younger than 40 yrs compared to the older ones. Consecutive FL cases from 4 different European centers (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) diagnosed in the last 25 yrs were retrospectively analyzed. For each patient data on clinical features at diagnosis, treatment and outcome were retrieved.

Results
A total of 1003 FL pts (452 males and 551 females; median age: 56.5 yrs, interquartile range 46–67 yrs) were collected, 153 of them were ≤40 yrs at the time of diagnosis. Comparing clinical features at diagnosis of pts >40 and of pts ≤40 yrs, some differences were observed. In younger pts there was a lower incidence of elevated LDH (14% vs. 23%, p=0.02), and a less frequent primary extra nodal localization (7% vs. 13%, p=0.03), but a more frequent bone marrow involvement (57% vs. 44%, p=0.003) and involvement of more than 4 nodal lesions (43% vs. 25%, p<0.001). Information concerning first line treatment was available for >95% of pts. At a median follow-up of 9.3 yrs (interquartile range, 5–15 yrs) 91% of pts ≤40 yrs have received treatment for their lymphoma, compared to 84% of pts >40 yrs (p=0.02). An initial wait and see policy was applied in 11% of the younger pts and in 19% of the remainder (p=0.03). No differences in the two populations were observed in the type of chemotherapy given as first FL treatment, but pts >40 yrs received more frequently rituximab, alone or in combination, than younger pts (26% vs. 13%, p=0.001).
At a univariate analysis younger pts had longer OS, and longer cause-specific survival (CSS, defined by deaths due to FL or acute toxicity of its treatment). In particular, the 10-yrs OS was 81% for pts ≤40 yrs (95%CI: 75–88%), vs 51% in the older ones (95%CI: 47–55%) (p<0.001). The 10-yrs CSS was 82% for pts ≤40 yrs (95%CI: 75–89%) compared to 60% in the older ones (95%CI: 56–64%) (p<0.001). 10-yr PFS was 39% for pts ≤40 yrs (95%CI: 31–48%), vs 24% in the older ones (95%CI: 21–28%) (p<0.001). Notably, when stratifying pts by age (≤40, 41–59 and ≥60 yrs) those ≤40 yrs-old at diagnosis had a CSS similar to that of pts of 41–59 yrs, but longer OS (figure 1). Even in this younger group, OS (median, 24 yrs) was, however, dramatically shorter than the life expectancy for the general population of the same age (approx. 45 yrs for males and 50 yrs for females in the UK, according to the Office for National statistics -www.statistics.gov.uk).
At multivariate analysis, the features at diagnosis significantly influencing OS and CSS were B symptoms, stage ≥III, hemoglobin<12 g/dl, elevated LDH, period of diagnosis (≤1990, between 1991 and 1999, and >2000), age>60 yrs.
No differences between age groups (≤40 yrs vs. >40 yrs) were observed in the incidence of second tumors (8% vs. 11%) and histological transformation (18% in both populations).

Conclusions
In this multicentre study younger pts with FL presented with different clinical features than those >40 yrs. As expected the CSS of pts >60 is strongly impaired, but interestingly the CSS of pts ≤40 yrs was similar to that of pts 41–59 yrs. Despite some limitations due to the fact that many pts were treated in the pre-rituximab era, these data suggest that FL still has a strong impact on survival duration of younger pts, who otherwise would have a long life expectation.

Disclosures:
No relevant conflicts of interest to declare.