Fu, Qianhong

Abstract Background The treatment (tx) landscape for chronic lymphocytic leukemia (CLL) has evolved, with National Comprehensive Cancer Network (NCCN) guideline-preferred novel therapies (NTs), such as acalabrutinib, zanubrutinib, and venetoclax-based regimens, now preferred over ibrutinib and chemoimmunotherapy (CIT) in front-line (1L) settings. We previously showed that patients (pts) from different racial/ethnic groups may not have equitable access to NTs. Here, we examined racial/ethnic inequities in 1L NT utilization among US pts with CLL and potential social determinants of health (SDOH) drivers of these inequities. Methods This retrospective cohort study utilized the US-based, electronic health record-derived de-identified Flatiron Health Research Database, linked to neighborhood (US Census track or block group) data from American Community Survey and Agency for Healthcare Research and Quality datasets. Eligible pts included adults with CLL who started 1L tx 01/01/2019-07/31/2024. The primary outcome was receipt of 1L therapy (CIT vs preferred NTs, ibrutinib vs preferred NTs), with NCCN guideline-preferred NTs (v2.2023-v3.2025) as a reference. Associations between race/ethnicity (White, Black, Hispanic) and 1L tx types were assessed using logistic regressions, adjusting for age, sex, year of 1L start, immunoglobulin heavy chain variable region status, and del17p/TP53 status. To better understand which SDOH factors contribute to racial and ethnic inequities in tx utilization, we performed mediation analysis using Multiple Mediation Analysis implemented through nonlinear multiple additive regression tree models. Individual-level (Eastern Cooperative Oncology Group status, practice type, insurance) and 20 area-level SDOH factors measuring social deprivation (defined as limited access to economic, social, neighborhood, physical, or healthcare resources) were assessed as potential mediators. Results Of the 4452 pts included in the study, 3717 were White (83%), 371 were Black (8%), 209 were Hispanic (5%), and 155 were Other race (4%). Black and Hispanic pts were more likely to live in neighborhoods with higher social deprivation, such as residential segregation (predominant race/ethnicity in the area: White, Black, Hispanic, Diverse), with no internet access, no vehicle ownership, and no health insurance coverage. Overall, 37% of pts received a preferred NT, highest among White (38%) pts, followed by Black (35%) and Hispanic (26%) pts. Compared with White pts, Hispanic pts were more likely to receive CIT than preferred NTs (adjusted odds ratio [aOR] 2.12; 95% confidence interval [CI] 1.46-3.09); Black (aOR 1.44; 95% CI 1.05-1.97) and Hispanic pts (aOR 1.83; 95% CI 1.17-2.85) were more likely to receive ibrutinib than preferred NTs. Pts living in areas with the highest social deprivation were less likely than their counterparts in lowest social deprivation neighborhoods to receive preferred NTs. Specifically, residence in predominantly Black or Hispanic neighborhoods (26% or 27% vs 39% predominantly White), areas with lowest socioeconomic status (32% vs 40%), and neighborhoods with the lowest levels of internet access (32% vs 39%), vehicle ownership (32% vs 39%), and health insurance coverage (34% vs 41%) was associated with lowest receipt of preferred NTs. In the mediation analysis, individual- and area-level SDOH factors explained 94.4% (95% CI 2.9-185.9) of the observed Black-White inequity in receipt of ibrutinib versus preferred NTs; residential segregation appeared to be the most important mediator (59.7%; 95% CI −3.5 to 123.0). Similarly, the Hispanic-White inequity in receipt of preferred NTs was driven by the combined effect of area-level SDOH and individual-level variables (88.5%; 95% CI 45.6-131.3), with residential segregation as the main driver (48.3%; 95% CI 10.7-85.9), followed by practice setting (9.8%; 95% CI −3.5 to 23.1). In contrast, measured SDOH factors did not explain the inequity in receipt of CIT versus preferred NTs between Hispanic and White pts (21.5%; 95% CI −8.3 to 51.4), suggesting that other factors may contribute to the observed inequities. Conclusion Black and Hispanic pts with CLL were less likely than White pts to receive preferred NTs. A significant proportion of these disparities was explained by area-level SDOH, particularly residential segregation. These findings underscore the need to address structural barriers to ensure equitable access to emerging, guideline-recommended treatments.

Abstract Background Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in US adults and incidence increases with age. Although the treatment (tx) landscape has evolved, it is unclear whether tx selection differs for older patients (pts), given concerns around comorbidities, toxicity, and efficacy. There is a need to better understand pt characteristics, tx patterns, and biomarker use among pts aged ≥65 yrs with CLL/SLL in the current therapeutic era. Methods A retrospective longitudinal study was conducted using the de-identified 100% Medicare Fee-for-Service (FFS) Research Identifiable Files. Included pts were diagnosed with CLL/SLL at age ≥65 and initiated first-line (1L) tx 1/1/2020-9/30/2024 (with ≥12 mo in database prior to 1L tx start). Index date was defined as date of 1L tx start, and pts were followed to death, end of Medicare enrollment, or study end, whichever occurred first. 1L tx was defined as any CLL pharmacologic tx within the first 90 days of index date. Tx utilization was summarized as the number and proportion of pts who received each tx at each line. Descriptive statistics were used to summarize demographic and social characteristics and baseline comorbidities, in all pts and by 1L tx. Proportion and timing of documented biomarker orders any time prior to index were summarized by test type (CLL fluorescence in situ hybridization [FISH], TP53 DNA sequencing and immunoglobulin heavy chain variable region [IGHV] test) and by 1L tx. Results Of the 21,008 pts included, median age was 76.4 yrs at 1L tx, with 43% of pts aged 65-74 yrs, 43% aged 75-84 and 14% aged ≥85. The majority of pts were male (58%) and White (91%). About 8% and 9% of pts had dual eligibility status and low-income subsidy, respectively. Median Charlson Comorbidity Index (CCI) was 4 (range: 1-21), with 40% of pts having CCI ≥5. Covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapies (mono) were most common at 1L tx (41%), including 10% zanubrutinib (zanu), 15% ibrutinib (ibr), and 16% acalabrutinib (acala). B-cell lymphoma 2 (BCL2)+anti-CD20 monoclonal antibody (mAb) was less common (11%), and chemoimmunotherapy (CIT) was used by 13% of pts, mostly BR (8%) and FCR (3%). Other less common tx included cBTKi+anti-CD20mAb (6%) or cBTKi+BCL2 therapies (1%). Among remaining pts, most received anti-CD20mAb (22%). The use of cBTKi mono increased from 41.7% in 2020 (ibr 30.6%; acala 11.1%) to 47.6% in 2024, driven by increased use of zanu (27.8%; acala 15.7%; ibr 4.2%). BCL2+anti-CD20mAb increased from 9.2% in 2020 to 12.6% in 2024. Pts treated with cBTKi mono were older than those with BCL2+anti-CD20mAb (median age 77.2 vs 74.5), and more likely to have dual eligibility status (10% vs 4%) or low-income subsidy (11% vs 5%). More pts who received zanu mono had CCI ≥5 (39%) versus acala (36%), ibr (35%), or BCL2+anti-CD20mAb (32%). Pts with BCL2+anti-CD20mAb were less likely to have diabetes (23% vs 26%), congestive heart failure (CHF; 16% vs 19%), chronic pulmonary disease (23% vs 27%), and renal diseases (23% vs 27%). Pts with ibr were less likely to have myocardial infarction (29% vs 34%), coronary artery disease (22% vs 25%), CHF (16% vs 19%), and atrial fibrillation (12% vs 18%). Overall, 69% of pts had FISH testing prior to 1L tx, but test orders for TP53 (12%) or IGHV (28%) status were infrequent. Pts with ibr had the lowest rates of TP53 tests (6%), whereas pts with CIT had the lowest rates of IGHV tests (16%). The timing of tests showed a binomial distribution where most pts received FISH, TP53, or IGHV tests either ≤60 days prior to 1L tx (46%, 50%, 33%), or >1 yr before 1L tx (30%, 22%, 43%). Among pts who received ≥2 lines of therapy for CLL (n=4428; 21%), cBTKi mono was the most common in 2L (41%), including 14% zanu, 17% acala, and 10% ibr. CIT and BCL2+anti-CD20mAb were used in 12% and 9% of pts, respectively. Only 634 (3%) pts had 3L+ tx, of whom 33% received cBTKi mono, including 16% zanu, 12% acala, and 5% ibr (5%). Conclusion This large real-world study found that cBTKi mono was the most common 1L tx choice among pts aged ≥65 with CLL/SLL, with increased use of next-generation cBTKi. Pts with more baseline comorbidities were less likely to receive ibr or BCL2-based tx. FISH testing was not performed in nearly one-third of pts, and most pts did not have TP53 or IGVH sequencing prior to tx. Future studies are needed to continue to evaluate evolving tx paradigms in older pts with CLL/SLL.

e13741 Background: The NCCN guidelines for first-line (1L) regimens in CLL have evolved over the past decade, shifting from ibrutinib (ibr) and chemoimmunotherapy (CIT) to second-generation BTK inhibitor and venetoclax combinations. We evaluated real-world use of preferred 1L treatment (tx) since 2016 in CLL patients (pts) in routine care to identify differences in prescribing based on race/ethnicity and practice type. Methods: This retrospective observational study utilized the US nationwide Flatiron Health electronic health record-derived de-identified database. Eligible pts had confirmed CLL and initiated 1L tx between 01/01/16-07/31/24. Primary outcome was receipt of preferred 1L tx defined by NCCN guidelines in four time periods by race/ethnicity (Hispanic, White, Black, Asian/Other). Odds ratios (ORs) were estimated using logistic regression, additionally adjusting for age, sex, ECOG performance status, IGHV, del17p/ TP53 mutation status, time period, and practice type. Results: A total of 7528 pts were included. Compared with White pts (n = 5472), Black pts (n = 640) were younger (median age at 1L: 68 vs 71). More Black and Hispanic (n = 290) pts were treated at community practices (86% vs 80% White). Of those pts tested, more Black pts had unmutated IGHV than White (77% vs 56%). Presence of del17p/ TP53 mutation was similar across races/ethnicities. The proportion of pts receiving preferred 1L tx based on the NCCN Guidelines significantly differed by race/ethnicity (Table) ( P = 0.0021). The proportion of Hispanic pts treated with preferred 1L tx was significantly lower than White (OR = 0.61; 95% CI: 0.47-0.79), but Black was similar to White (OR = 1.07; 95% CI: 0.89-1.30). Updates to NCCN guidelines were significantly associated with pts receiving preferred 1L tx by practice type ( P = 0.0005). In 2016-2018, 44% of community practices and 55% of academic centers adopted targeted therapies (TTs); in 2019, ibr use increased in both practices (77% vs 68%, respectively). Adherence to preferred tx improved across practices in 2020 but decreased with the prioritization of second-generation therapies. After the approval of zanu, use of TTs was 71% in community practices and 74% in academic centers. Conclusions: Inequities in pts with CLL receiving preferred 1L tx suggests disproportionate use of CIT and ibr by race/ethnicity. Use of preferred TTs also differed by practice type and time period, with increased adoption after pivotal trials. Time period % Pts receiving preferred tx by race a White Black Hispanic Asian/Other 2016-2018:Preferred tx ibr 46% 50% 43% 45% 2019(v2.2019: Jan 2019)Preferred tx ibr 76% 76% 67% 79% 2020-Jun 2022(v4.2020: Feb 2020)Preferred tx acala, VO, ibr 84% 84% 69% 83% Jul 2022-Jul 2024(v2.2023: Aug 2022)Preferred tx acala, VO, zanu 72% 66% 56% 73% VO, venetoclax + obinutuzumab. a By listing of NCCN preference (preferred vs other) among non-del17p and age >65.