Durani, Urshila

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare but aggressive non-Hodgkin lymphoma with limited prospective data to guide optimal therapy. This study evaluates real-world treatment patterns and survival outcomes using a large national cohort. Methods We analyzed data from the National Cancer Database (NCDB) for patients diagnosed with PCNSL between 2004 and 2020. Baseline demographics and treatment characteristics were analyzed using descriptive statistics. Survival outcomes were estimated using the Kaplan-Meier method and compared using log-rank tests. Multivariable Cox proportional hazards models were constructed to identify independent predictors of overall survival (OS). Results A total of 14,450 patients with PCNSL were included; 14,439 had first-line treatment data available, and 13,390 had survival data. Median age at diagnosis was 67 years (range 18-90), 49.2% were female, and 6.6% were African American. Chemotherapy alone was the modality of treatment for 81.6% (n=11,787), 12.2% (n=1,769) received chemoradiation, 3.8% (n=545) received chemotherapy and underwent autologous stem cell transplant (ASCT) but no radiation, and 2.4% (n=348) received radiation only. The median follow-up time was 73.5 months (95% CI 71.4-75.6), and the median OS for the group was 17.4 months (95% CI 16.2-18.6). Survival differed significantly by age group (median OS: <65 yrs, 46.1 months [95% CI 41.7 -50.6]; 65-79 yrs, 12.5 months [95% CI 11.2-13.7]; ≥80 yrs, 3.2 months [95% CI 2.9-3.5]; p<0.001), by year of diagnosis (median OS: 2004-2009, 11.0 months [95% CI 9.9-12.1]; 2010-2015, 20.0 months [95% CI 17.4-22.6], 2016-2020, 29.7 months [95% CI 26.0-33.4]; p<0.001), and by frontline treatment strategy (p<0.001). Patients treated with chemotherapy followed by ASCT had the longest median OS (not reached), while those receiving radiation alone had the poorest outcomes with a median OS of 3.9 months (95% CI 3.2-4.7); chemoradiation patients had a median OS of 31.8 months (95% CI 27.5-36.1), and chemotherapy only patients had a median OS of 13.9 months (95% CI 12.7-15.1)(p<0.001). African American patients had an inferior outcome with a median OS of 10.2 months [95% CI 7.2-13.1], compared to “other” races with a median OS of 36.9 months [95% CI 27.6-46.1] (p<0.001), although this is more similar to the median outcome for white patients (17.0 months [95% CI 15.8-18.3]). Treatment at an academic center (25.7 vs 11.0 months) and a high case-volume center (defined as >median number of cases per facility) (18.6 vs 10.5 months), and lower Charlson-Deyo comorbidity scores (CDS) (defined as CDS 0-1) (21.7 vs 6.8 months) were also associated with superior OS (p<0.001). In multivariable analysis, increasing age ( 65-79 y.o HR 1.60 [1.52-1.1.68], ≥80 y.o HR 2.95 [2.75-3.17]), CDS≥2 (HR 1.36 [1.28-1.44]), and African American race (HR 1.12 [1.02-1.24]) were adverse predictors of OS (all p<0.001), while treatment strategy (ASCT [HR 0.17], chemoradiation [HR 0.53], chemotherapy only [HR 0.68] compared to radiation alone), more recent year of diagnosis (2010-2015 [HR 0.81], 2016-2020 [0.70]), and treatment at an academic center [HR 0.81] remained predictors of superior OS (all p<0.001). Conclusion In this large national cohort of patients with PCNSL, treatment with chemotherapy followed by ASCT was associated with the most favorable survival outcomes. Patients treated with chemoradiation or multi-agent chemotherapy also demonstrated improved survival compared to those receiving radiation monotherapy or single-agent chemotherapy alone, respectively. Age, comorbidities, race, and treatment at academic centers were also significant independent predictors of OS. These findings highlight substantial disparities in outcomes and underscore the importance of optimizing treatment strategies, improving access to high-intensity therapies, and supporting timely referral to academic or high case-volume centers, particularly for younger and medically fit patients.

207 Background: CAR-T & bispecific antibodies (BsAb) for large B-cell lymphoma offer deep responses, but have unique toxicities requiring close monitoring. Different practice settings have varied strategies for managing these toxicities, leading to increased costs, healthcare resource use, & reduced quality of life. With no direct comparison, rationale for therapy selection may vary. This study explores provider choices, sequencing strategies & access barriers. Methods: A survey of US-based Hematologists was conducted on practice demographics, therapy availability, preferences, & barriers in LBCL. Responses were analyzed across clinical scenarios. Results: Responses were received from 45 physicians. Availability of CAR-T & BsAb varied with 75% prescribing both, & only BsAb being available at 9% of providers’ centers. There was a strong preference for CAR-T over BsAb—higher among academic vs. nonacademic providers (96% vs. 78%; p = 0.03) & at CAR-T vs. non-CAR-T centers (100% vs. 72%; p = 0.001). Even at BsAb-only centers, preference leaned toward CAR-T, though notably lower compared to CAR-T centers. Among centers without either, 86% preferred CAR-T. Practice volume had no impact. Reasons for favoring CAR-T included perceived better outcomes (55%), shorter treatment (26%), center choice (19%), more experience (48%), & curative potential (21%). BsAb selection was driven by CAR-T unavailability & logistical barriers (distance to specialized center, insurance delays, referral complexity, manufacturing time, & hospitalization needs). Axi-cel was preferred by 69% ( p = 0.0001) vs. other CAR-T for third-line or later due to experience with use, response rates, center choice, & logistical ease. Liso-cel (26%) & Tisa-cel (2%) were chosen for perceived favorable toxicity over Axi-cel. Axi-cel was also preferred second-line vs. Liso-cel (73% vs. 24%; p < 0.0001) for similar reasons. Among BsAb, Epcoritamab was favored by 56% for administration ease (subcutaneous), experience, & center preference; Glofitamab by 42% for shorter duration, experience, & center preference. There was no difference by academic vs nonacademic practice & volume for both CAR-T & BsAb. In patients with prior non-CAR-T anti-CD19 therapy, providers chose CD19 CAR-T over CD20 BsAb (80% vs. 18%; p < 0.0001). For relapse after second-line CAR-T, 78% providers preferred BsAb as the next line over other options ( p < 0.0001) due to more favorable response rates, toxicity profile, & experience with use. Providers prioritized response rates, survival, & toxicity profile in their treatment decisions. Logistics, duration, frequency, & cost were less important. There were no differences based on practice setting & CAR-T experience. Conclusions: Despite higher preference for CAR-T due to perceived superior outcomes, access barriers exist. Efforts to streamline referral pathways, logistics, & expand availability are crucial to improve outcomes.

e13738 Background: Persistent racial/ethnic and regional disparities in neoplasm mortality remain significant public health challenges. This study evaluates long-term trends in neoplasm mortality by race/ethnicity at the county level in the United States and examines the relationship between hospital density and mortality. Methods: Using data from the Global Burden of Disease Study (2000-2019), we analyzed age-standardized mortality rates (ASR) for neoplasms by ethnicity/raceHispanic (all races) and non-Hispanic American Indian or Alaska Native (AIAN), Asian or Pacific Islander (API), Black, and White. A joinpoint regression analysis was used to identify significant changes in the mortality trends, summarized as average annual percent change (AAPC). Correlation analysis evaluated the relationship between county-level hospital density and neoplasm mortality. Results: Neoplasm mortality rates declined across all racial/ethnic groups from 2000 to 2019, but disparities persisted. ASR per 100,000 population decreased from 240.5 (95% UI: 214.3–269.9) to 203.0 (180.8–228.3) for AIAN, 149.5 (144.9–153.9) to 115.3 (111.7–118.7) for API, 314.5 (312.1–317.0) to 218.7 (217.1–220.3) for Black, 168.4 (164.6–172.0) to 133.8 (131.0–136.4) for Latino, and 241.2 (240.5–242.0) to 187.5 (186.9–188.2) for White. AAPC from 2000 to 2019 ranged from -0.94% (AIAN) to -1.90% (Black). Gender-specific analyses revealed similar trends, with males showing slightly greater declines. Southeast states experienced slower declines compared to the Northeast. Some counties exhibited worsening mortality trends, particularly for AIAN, API, and Latino. The county-level hospital density (table) showed weak but statistically significant correlations in 2019 for AIAN (r = -0.35; p < 0.0001), White (r = -0.15; p < 0.0001), and Black (r = -0.18; p < 0.0001). No inverse correlation was observed for API (r = 0.07; p = 0.071) and Latino (r = 0.06; p = 0.012). Conclusions: While significant progress has been made in reducing neoplasm mortality, racial/ethnic and regional disparities persist, and health care access appears to contribute to this at least in part. Future analyses should evaluate mortality by cancer site and also account for broader clinical and public health infrastructure, as well as social determinants of health to better understand and address underlying disparities. The correlation between hospital density and age-standardized mortality rate from neoplasms by race/ethnicity in 2019. Correlation coefficient with mortality and hospital density AIAN API Black Latino White 2019 -0.35(-0.43 – -0.27) 0.069(-0.0058–0.14) -0.18(-0.23 –-0.13) 0.064(0.014–0.11) -0.15(-0.19 – -0.12)

7075 Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive peripheral T-cell lymphoma arising primarily from γδ T-cells. It carries a poor prognosis and resists conventional chemotherapy. Most reports on HSTCL are case-based. This study comprehensively analyzes a large cohort, evaluating treatment strategies and survival outcomes. Methods: This retrospective study included patients (pts) with pathologically confirmed HSTCL diagnosed between 2000-2024, consecutively seen at Mayo Clinic MN. Clinical, pathological, genomic, and treatment-related data were extracted when available. Descriptive statistics were used to summarize baseline characteristics. Time-to-event analyses, including Kaplan-Meier estimates, median overall survival (OS), and survival time estimates were conducted from the date of diagnosis. Results: A total of 20 patients with newly diagnosed HSTCL were included, with a median age of 57 years (range: 35-71). The cohort was predominantly male (70%) and non-Hispanic (93%). Molecular data was available for five patients, revealing abnormalities in STAT5B, MLL3 deletion, TP53, EZH2, TERT, and NF1 E291D . The median follow-up was 27.6 months (m) with a median OS of 17.6 m (95% CI: 11.2 - NA). First-line treatment was anthracycline-based in 68% of pts and non-anthracycline-based in 32%, with higher response rates in the latter group (50% vs.83%). Although non-anthracycline regimens showed a trend toward improved 3-year OS (100% vs. 29%) the difference was not statistically significant (p = 0.16). Achieving a complete response to first-line therapy was also associated with a trend towards a better 3-year OS compared to refractory disease (80% vs. 50%, p = 0.17). Most pts (79%) underwent hematopoietic stem cell transplant (HSCT), primarily allogeneic, with only one receiving autologous HSCT. First-line therapy before HSCT was evenly distributed between anthracycline (55%) and non-anthracycline (45%) regimens. HSCT recipients had significantly higher 3-year OS than non-recipients (83% vs. 33%, p = 0.017). Notably, the patient with a TP53 mutation has remained in remission for over a year post-allogeneic HSCT. Conclusions: HSTCL predominantly affects younger pts, with nearly half dying within a year. Allogeneic HSCT, rarely used in other NHL subtypes, improved survival. Non-anthracycline regimens and achieving CR trended toward better outcomes. Our study, leveraging a sizable cohort, highlights the need for targeted research and novel therapies to improve HSTCL management. Summary of survival outcomes in HSTCL. Characteristics Median OS (y) 3-Year OS (95% CI) 1.48 [0.93- NA] 46% [0.26 - 0.81] Transplant Transplant NA [NA - NA] 83% [0.58 - 1.00] No Transplant 1.02 [0.93 - NA] 33% [0.07 - 1.00] Treatment Anthracycline Based 1.02 [0.36 - NA] 29% [0.11 - 0.73] Non-Anthracycline Based 4.61 [NA- NA] 100% [1.00 - 1.00]

7032 Background: The impact of immune cell counts pre LD and during immune reconstitution on CAR T therapy outcomes is poorly understood. We investigated the association between CD4, CD8 and NK cell counts and CAR T therapy outcomes in patients with LBCL. Methods: Retrospective study of R/R LBCL patients who received CAR T cells between 2016-24 at Mayo Clinic, Rochester, were included in this analysis. Peripheral blood CD4, CD8 and NK counts were measured pre LD and at M1 post CAR T infusion. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff for pre LD and M1 immune cells to predict patients who were alive and in remission at 6 months (M6) post CAR T infusion. Patients who progressed or were lost to follow up prior to day 30 were excluded from M1 ROC analysis. Results: Of 140 patients, 81 were alive and in remission at M6 (Group A), while 59 had relapse or death (Group B). Axicabtagene ciloleucel was the CAR T product given in 81% of patients (114/140). Median pre LD CD4 counts were significantly lower in Group B compared to group A (143 vs 280 cells/µL, p = 0.001). No significant difference was observed in median pre LD CD8 counts (205 vs 221 cells/µL, p = 0.8). ROC analysis identified an optimal pre LD CD4 count of 124.5 cells/µL for M6 alive+remission. Lower pre LD CD4 counts (<124.5) predicted worse progression free survival (PFS) in univariate (HR = 3.02, 95% confidence interval [CI]: 1.73–5.27, p< 0.01) and multivariable analysis (MVA) adjusted for IPI and the number of prior lines (aHR = 2.54, 95% CI: 1.39–4.62, p< 0.01).Lower pre LD CD4 counts also predicted inferior overall survival (OS) in MVA (aHR = 2.27, 95% CI: 1.08–4.77, p = 0.03). (Table 1) On day 30 landmark analysis, ROC identified M1 optimal CD4 count of ≥ 99.5 cells/µL to be associated with a trend toward superior PFS (P=0.09), but not OS (p=0.90) in MVA. Median pre LD NK cell counts were significantly lower in Group B (73 vs 98 cells/µL, p = 0.04). ROC analysis identified an optimal pre LD NK count of 151 cells/µL for M6 alive + remission. Lower pre LD NK counts (<151) predicted worse PFS, both on univariate (HR = 4.17, 95% CI: 1.29–13.47, p = 0.02) and MVA (aHR = 4.64, p< 0.01). The lower pre LD NK cell count group had worse OS in MVA (aHR = 5.69, 95% CI: 1.16–28.1, p = 0.01). (Table 1) On D30 landmark analysis, M1 NK cell count of ≥ 128.5 cells/µL was associated with a trend toward superior PFS (P=0.08), but not OS (p=0.30) in MVA. Conclusions: Pre LD CD4 and NK cell counts are significantly associated with PFS and OS post CAR T therapy in patients with R/R LBCL. Pre-treatment immune subset levels may identify patients at higher risk of relapse or death after CAR-T therapy. Groups Median PFS 2 Year PFS Median OS 2 Year OS CD4 ≥124.5 cells/µL (N=75) NR 58% 3.31 years 67% CD4 <124.5 cells/µL (N=30) 2.2 months 22% 1.59 years 45% NK ≥151 cells/µL (N=17) NR 77% NR 84% NK <151 cells/µL (N=82) 10.6 months 44% 3.31 years 62%