Hematologic Toxicity Among Real-World US Patients with Follicular Lymphoma Treated with Tazemetostat Compared to Other Standard-of-Care Therapies
Authors: Dennen Syvart , Dillon Allison , Cockrum Paul , Kambhampati Swetha 
Published: December 2024

BACKGROUND: While follicular lymphoma (FL) is generally an indolent disease, its relapsing and remitting course can require multiple lines of therapy (LOTs). Over the last decade, a better understanding of the molecular pathogenesis of FL has led to the emergence of novel therapies, particularly in later lines. Tazemetostat (taz) is an oral medication approved as monotherapy (mono) for patients (pts) with R/R FL with EZH2 gain-of-function mutations who received at least 2 prior systemic therapies or R/R FL pts who have no satisfactory alternative treatment options.
The range of treatments for R/R FL each come with their own profile of toxic effects. Treatments with fewer adverse events (AEs) reduce healthcare resource utilization (HCRU) and have the potential to improve pt quality of life (QoL). We describe rates of hematologic AEs and granulocyte colony-stimulating factor (G-CSF) use using real-world (RW) data from the US, focusing on third-line (3L) and fourth-line (4L) therapies. In addition, we report results for taz mono pts, describing a pt group of unknown line to allow sufficient sample size.
METHODS: This retrospective, observational study used Optum Market Clarity claims and electronic health record (EHR) data, which contains 93% encounters at confirmed community facilities in the US. Non-taz pts were included if they had ≥1 inpatient or ≥2 outpatient claims or ≥1 EHR record with a diagnosis of FL from January 1, 2008 to December 31, 2023 (index date); ≥12 months pre-index continuous enrollment or EHR clinical activity with no evidence of cancer; 3L or 4L initiated after January 1, 2015; ≥1 EHR record on or after 3L/4L treatment initiation.
For taz mono pts, modified inclusion criteria were employed to allow sufficient sample for analysis: ≥1 diagnosis of FL in claims or EHR data; ≥1 taz fill in claims or EHR; and ≥1 EHR record on or after first taz fill. Due to the limited criteria, taz mono pts may have additional cancers, could not be assigned a LOT, and may have been observed during a LOT in progress. Based on indication, taz mono pts are expected to be predominantly in 3L and 4L.
Hematologic AEs (anemia, neutropenia, and thrombocytopenia) were identified using lab values in EHR or claims data and graded according to the Common Terminology Criteria for AEs v5.0. G-CSF administrations were measured using both claims and EHR data. Results of ≤4 pts are not reportable per Optum rules; these are reported as ≤[percentage]. Due to this rule, all grades of AEs are combined to increase reportable figures.
Regimens were categorized based on clinical input. Rituximab (R) + chemo consists of R-CHOP, R-CVP, R-ICE, or similar, excluding R + bendamustine (B). Chemo includes mono or combination treatment with platinum-based therapies, cytarabine, vincristine, and similar. Results are reported for categories with ≥40 pts. This analysis was descriptive only; no adjustments for pt characteristics and no statistical testing was performed.
RESULTS: There were 50 taz mono pts of unknown LOT, while there were 993 pts in 3L treatment categories with ≥40 pts. We present the sample size for each category followed by the percentage with any grade anemia, neutropenia, thrombocytopenia, and ≥1 G-CSF use during the line: taz mono (n=50, 28%, 10%, ≤8%, ≤8%), R mono (n=507, 16%, 6%, 3%, 2%), R + chemo (n=162, 56%, 33%, 30%, 67%), chemo (n=109, 41%, 18%, 18%, 32%), R + B (n=101, 32%, 17%, 15%, 51%), BTKi-containing (n=64, 47%, 20%, 22%, 8%), and R2 (n=50, 50%, 30%, 18%, 16%).
In the 4L of our analysis, there were 517 pts in treatment categories of ≥40 pts. The 4L categories and results, with taz mono repeated, are: taz mono (n=50, 28%, 10%, ≤8%, ≤8%), R mono (n=288, 15%, 6%, 2%, ≤1%), chemo (n=69, 48%, 23%, 25%, 28%), R + chemo (n=63, 68%, 32%, 40%, 68%), R + B (n=55, 31%, 16%, 13%, 38%), and BTKi-containing (n=42, 43%, 29%, 29%, 17%).
CONCLUSIONS: Taz mono was most numerically comparable to R mono in rates of hematologic AEs and G-CSF use and had numerically lower rates of each than all other regimens. In most cases, the differences were clinically meaningful. The reduced hematologic toxicity observed with taz mono combined with its oral formulation may be helpful to consider when selecting treatment for FL pts, depending on their personal circumstances. Further research should evaluate rates of AEs adjusted for pt characteristics, the RW effectiveness of taz, and its impact on pt QoL compared to other standard-of-care therapies (SOC) in a real-world setting.