Treatment Patterns and Outcomes Among Patients with Relapsed/Refractory Follicular Lymphoma Treated in Routine Clinical Practice in the US with Three or More Lines of Therapy
Authors: Ta Jamie T. , Arndorfer Stella , Julian Cristina , Wu Mei , Lai Dominic , Shapouri Sheila 
Published: November 2021

Abstract
Background: Follicular lymphoma (FL) is an indolent, yet incurable disease, and patients often require several lines of therapy throughout their lifetime (Batlevi et al. Blood Cancer J 2020); however, there are limited real-world data available regarding the treatment of a contemporary cohort of patients with relapsed/refractory (R/R) FL. The objective of this study was to assess real-world treatment patterns and outcomes among patients receiving third- and later-line (3L+) therapies for FL in the US.
Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. During the study period, de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. We selected patients aged ≥18 years with an initial FL diagnosis between January 2011 and January 2021, who had received at least 3 lines of therapy for FL (follow-up ended March 2021). Exclusion criteria included: evidence of clinical trial participation during the study period, high-grade (3b) FL at diagnosis, transformation to an aggressive lymphoma any time before 3L FL treatment, or other anticancer therapies or stem cell transplant 12 months before first-line (1L) FL treatment. Patient demographic and clinical characteristics were assessed using descriptive statistics. Treatment patterns and time to next anti-lymphoma treatment or death (TTNTD) were reported. Median TTNTD was estimated using Kaplan-Meier methods.
Results: Of 2,990 patients receiving treatment for FL during the study period, 157 patients who received at least 3 lines of therapy for FL were included. Median age at time of 3L FL treatment initiation was 70 years, and 48.4% (n=76) of patients were male. At initial FL diagnosis, 79.6% (n=125) had low-grade (1-2) FL, 78.3% (n=123) had advanced stage (III/IV) FL, and 68.6% (n=48) of the 70 patients with available Follicular Lymphoma International Prognostic Index (FLIPI) scores had high-risk FLIPI (≥3). Overall, 68.2% of patients had evidence suggestive of early progression of disease within 24 months of 1L FL treatment. The majority of patients were treated at community oncology practices (n=140 [89.2%]). Median time to 3L treatment initiation from diagnosis was 35.6 months, and median follow-up after 3L treatment was 15.4 months. Fifty-two (33.1%) patients received a subsequent fourth-line therapy. The most common 3L treatment regimens received were rituximab (R) monotherapy (n=32 [20.4%]), R plus bendamustine (n=26 [16.6%]), R plus lenalidomide (n=18 [11.5%]), obinutuzumab monotherapy (n=14 [8.9%]), and idelalisib (n=13 [8.3%]; Table). Median TTNTD after 3L treatment was 14.1 months (95% confidence interval: 10-23.6; Figure).
Conclusions: Our study provides an update on the heterogeneous treatment landscape for R/R FL in the US for patients receiving 3L+ therapy in real-world clinical practice, the majority of whom were treated in community oncology practices. Many patients requiring 3L+ FL treatment had clinical characteristics predictive of poor prognosis, as evidenced by the high proportion of patients who had evidence of early progression and high-risk FLIPI at diagnosis. Treatment outcomes following 3L therapy remain poor, and approximately one-third of patients required additional treatment beyond 3L. Limitations of this analysis include those inherent to real-world observational databases and the relatively short follow-up of patients with indolent FL in the Flatiron Health database, particularly following 3L FL treatment. Future studies with additional follow-up are warranted. Nevertheless, these findings highlight the ongoing unmet need for novel, effective treatments in this setting in order to improve patient outcomes.
Figure 1 Figure 1.

Disclosures
Ta: Genentech, Inc.: Current Employment. Arndorfer: Genesis Research: Consultancy, Current Employment. Julian: Genentech, Inc.: Current Employment, Current holder of stock options in a privately-held company. Wu: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Lai: Bristol-Myers Squibb: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Shapouri: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment.