Changes in Treatment Patterns over Time Among Real-World Patients with Follicular Lymphoma at Predominantly Community Facilities in the US
Authors: Kambhampati Swetha , Dillon Allison , Cockrum Paul , Dennen Syvart 
Published: December 2024

BACKGROUND: Follicular lymphoma (FL) is characterized by a relapsing and remitting course that can lead to multiple lines of therapy (LOTs). While frontline treatments are well-established, optimal treatment in third line (3L) or later is not well-defined and the introduction of novel therapies in recent years has increased treatment options. This study examines changes in treatment patterns over the time periods of 2015-2018 and 2019-2023 for first (1L) through fifth line (5L) among US real-world FL patients (pts).
METHODS: This retrospective, observational study used Optum Market Clarity claims and electronic health record (EHR) FL data, which has 93% encounters from confirmed community facilities in the US. Inclusion criteria were: ≥1 inpatient or ≥2 outpatient claims or ≥1 EHR record with diagnosis of FL from 2008-2023 (index date); ≥12 months pre-index enrollment or EHR clinical activity with no evidence of cancer; ≥1 LOT initiated in 2015 or later.
LOTs consist of all therapies administered in the first 28 days of treatment. Adding new therapies after this period initiated a new LOT. Maintenance lines were excluded from analysis. This study is descriptive only and no statistical testing was performed.
RESULTS: In 1L, there were 2906 pts from 2015-2018 and 1878 from 2019-2023. Most treatments were rituximab (R)-based and changed little over time. For 2015-2018 vs 2019-2023, &gt;80% of treatments were either R + chemo (consisting of R + bendamustine, R-CHOP, R-EPOCH, R-ICE, and similar therapies) (61% vs 58%) or R monotherapy (mono) (28% vs 25%). Chemo (mono or combination treatment with platinum-based therapies, cytarabine, vincristine, and similar), the third largest category, was unchanged (5% vs 5%). Small increases were seen in ofatumumab (OF) or obinutuzumab (OB) + bendamustine (2% vs 5%) and R + lenalidomide (R2) (1% vs 2%). Utilization of other therapies was uncommon.
In 2L there were 1300 pts from 2015-2018 and 956 from 2019-2023. R-based regimens were the most common, but were less utilized and had larger decreases between time periods than in 1L. For 2015-2018 vs 2019-2023, decreases were seen in R mono (41% vs 34%) and R + chemo (35% vs 31%). Increases were seen in R2 (2% vs 6%), OF and OB mono or with bendamustine (3% vs 7%), and lenalidomide or venetoclax mono (2% vs 5%).
In 3L, there were 614 pts from 2015-2018 and 497 from 2019-2023. R mono was the most common therapy but dropped between periods (41% vs 28%). R + chemo decreased slightly (23% vs 21%) as did PI3Ki-containing (5% vs 2%). Similar over time were chemo (10% vs 10%) and BTKi-containing (7% vs 8%). Increases were seen in OF and OB monotherapy (1% vs 4%), R2 (5% vs 7%), lenalidomide or venetoclax mono (3% vs 9%), CAR-T (0% vs 2%), and tazemetostat (taz)-containing (0% vs 2%).
In 4L, there were 344 pts from 2015-2018 and 288 from 2019-2023. As in 3L, R mono was the most common therapy but dropped between periods (46% vs 28%), while R + chemo showed a small decrease (20% vs 17%). Similar over time were PI3Ki-containing (5% vs 5%), and R2 (3% vs 4%). Chemo (11% vs 13%) increased slightly, and increases were also seen in BTKi-containing regimens (7% vs 11%), OF or OB mono (0% vs 4%), lenalidomide or venetoclax mono (3% vs 8%), CAR-T (0% vs 2%), and taz-containing (0% vs 2%).
In 5L, there were 180 pts from 2015-2018 and 149 from 2019-2023. R mono was the most common therapy, with utilization dropping between periods (56% vs 32%). Similar across time were R + chemo (12% vs 13%), BTKi-containing (9% vs 10%), and PI3Ki-containing (4% vs 3%). Increases were seen in lenalidomide or venetoclax mono (4% vs 13%), chemo (6% vs 9%), R2 (3% vs 7%), CAR-T (0% vs 3%), and taz-containing (0% vs 3%).
While mosunetuzumab, a bispecific monoclonal antibody (bsAb), was approved in late 2022, there were not sufficient pts to assess utilization.
CONCLUSIONS: R-based regimens, particularly R mono, continue to be the mainstay of FL treatment in US community facilities. While 1L treatments changed little over time, in later lines, R mono use decreased, replaced by more novel therapies such as R2, BTKis, OF, OB, lenalidomide, venetoclax, taz, and CAR-T. Utilization of newer therapies in later lines in the community remains low, with the standard treatments of R mono and R + chemo making up 44% to 65% of treatments in 2L-5L during 2019-2023. Future research should evaluate use of other novel therapies such as bsAbs and the impact of later line sequencing on clinical outcomes.