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Abstract Background: Splenic Marginal Zone Lymphoma (SMZL) is a rare B-cell lymphoma with heterogeneous clinical behavior. Although typically indolent, survival outcomes are modestly inferior to those of other indolent lymphomas, with 5-year overall survival (OS) rates of 70–80% compared to 85–95% in follicular or nodal marginal zone lymphoma. Additionally, 5–10% of patients present with aggressive disease, highlighting the need for better prognostic tools and treatment strategies. While rituximab (RTX) has become central to SMZL management, often replacing splenectomy as first-line therapy, it remains unclear whether survival outcomes have improved during this era of increased RTX use. We conducted a national analysis to characterize treatment patterns, prognostic factors, and survival trends over time. Methods: We conducted a retrospective cohort study of SMZL cases diagnosed between 2004 and 2020 using the National Cancer Database (NCDB). Descriptive statistics characterized baseline features. OS was estimated via Kaplan-Meier methods and compared using log-rank tests. Cox proportional hazards models assessed prognostic factors. To evaluate changes in survival over time, we stratified cases by year of diagnosis into early (2004–2009), mid (2010–2014), and recent (2015–2020) RTX-era cohorts. Differences in survival between eras were compared using the log-rank (Mantel–Cox) test. Results: Among 7,228 patients with SMZL, treatment data were available for 7,176 (99.2%). Median age at diagnosis was 69 years (IQR: 60 to 77), with 4.9% identifying as African American. Of 4,167 patients with stage data, 64% had advanced-stage (III or IV) disease. Among patients with available risk scores, 37% were classified as high-risk by IPI (4-5) and 43% had a Charlson-Deyo (CD) comorbidity score of 3 or higher. Treatment patterns included splenectomy alone in 1,381 patients (19%), RTX monotherapy in 2,068 (28.5%), and combined RTX and splenectomy in 3,727 (51.9%). Chemotherapy was administered to 1,834 patients (25%), radiation to 29 (0.4%), and autologous transplant to 3. Treatment modalities overlapped due to multimodal approaches; Patients undergoing splenectomy tended to be younger (≤65 years), have earlier-stage disease, lower CD scores, and low-risk IPI (all p < 0.001). Sixty-eight percent received care at academic centers. Median follow-up was 130 months (95% CI: 123.2 to 136.4). Three- and five-year OS rates were 81.5% and 73.6%, respectively. Despite increased RTX use over time, no significant improvement in OS was observed across eras (log-rank p = 0.35). Survival varied significantly by treatment strategy (p < 0.001). Patients who received neither RTX nor splenectomy had the poorest outcomes, with a median OS of 19.3 months (95% CI not estimable to 70.7). Splenectomy alone was associated with the longest median OS of 148.8 months (95% CI: 137.9 to 159.7), though this likely reflects favorable patient selection. Median OS was not reached for RTX monotherapy patients, suggesting similarly favorable, if not superior long-term outcomes. Combined RTX and splenectomy were associated with similarly prolonged survival (median OS 119.4 to 120.6 months). Addition of chemotherapy in sequential treatment did not significantly affect OS (121 vs. 131 months; p = 0.07). On multivariable analysis, factors independently associated with inferior OS included older age at diagnosis (HR 1.07; 95% CI: 1.06–1.08; p < 0.001) and higher CD comorbidity score (HR 1.29; 95% CI: 1.18–1.42; p < 0.001). In contrast, female sex (HR 0.66; 95% CI: 0.56–0.78; p < 0.001), treatment at an academic center (HR 0.84; 95% CI: 0.71–0.99; p = 0.04), and receipt of RTX (HR 0.48; 95% CI: 0.32–0.74; p < 0.001) were associated with prolonged OS. Conclusion: In this large national cohort of SMZL, receipt of RTX, alone or with splenectomy, was associated with improved OS. Favorable prognostic factors included younger age, female sex, lower comorbidity burden, and treatment at academic centers. However, despite greater RTX use over time, population-level survival in the recent RTX era has not significantly improved, likely reflecting poor outcomes in relapsed or refractory disease. These findings highlight the need to optimize frontline therapy and develop novel strategies to improve long-term outcomes in SMZL.

Abstract Introduction: NAVD has become a standard-of-care for frontline (1L) treatment (tx) of advanced stage cHL, based on the results of the S1826 study. S1826 demonstrated a 1-year progression free survival (PFS) of 94% for NAVD compared to 86% for brentuximab vedotin-AVD, which remained durable at 2 years (Herrera et al, NEJM 2024). Adverse events (AEs) and efficacy have not been reported in patients (pts) treated with NAVD outside of a clinical trial. Hence, we sought to evaluate safety profile and efficacy outcomes of pts with cHL treated with 1L NAVD in a real-world setting (RWS). Methods: In this multicenter retrospective cohort study, we included pts ≥18 years with cHL treated with 1L standard of care NAVD between 2023 and 2025 at 20 US academic sites. The safety evaluable cohort received at least 1 cycle of NAVD and included pts who have not completed tx. The efficacy evaluable cohort had completed 6 cycles of tx including end of treatment (EOT) PET-CT and included pts who intended to complete tx but died or discontinued due to progressive disease or AEs. The primary endpoint was EOT overall response rate (ORR). Secondary endpoints included EOT complete response rate (CRR), PFS and overall survival (OS). PFS and OS were calculated from the start date of tx and analyzed using the Kaplan Meier method. Results: A total of 311 pts with cHL were treated with NAVD with 26% of pts with tx ongoing (n=83) and 73% with tx completed (n=228). Baseline demographics included 55% male pts, 60% with stage IV disease (stage IIB, n=4) and 84% with nodular sclerosis subtype. Median age was 37 years (range 18-88), 29% had bulky disease (>7.5 cm), 28% were EBV positive (n=74/268), 8% had history of an autoimmune disease, and 31% had an IPS 4-7. G-CSF was given in 64% of pts. All patients were safety evaluable. Tx was interrupted (any length) in 24%, reduced in 12%, and discontinued in 14%. The most common reason for dose reduction was neuropathy in 4%. Nivolumab was discontinued in 10% and all therapy in 3.7% due to toxicity. Any AE and any grade 3 or higher AE (>G3) were observed in 92% and 62%, respectively. Neutropenia of any grade occurred in 68% (48% >G3), infection in 25% (10% >G3), and neuropathy in 30% (2.8% >G3). Hospitalization for an AE occurred in 20% (4.5% febrile neutropenia). Among pts with complete data (n=305), any immune related AE (irAE) occurred in 78 pts (25.6%) with any >G3 irAE in 23 pts (7.5%). The most common irAEs included hypothyroidism (7.9%, all grade 1-2), hepatotoxicity (1.6% G1/G2, 3.3% >G3), inflammatory arthritis (3% G1/G2, 0.6% >G3), rash (2.6%, all grade 1-2), and colitis (1% G1/G2, 1% >G3). Other notable >G3 irAEs included adrenal insufficiency (n=2), AKI/ATN (n=1), myocarditis (n=1), diabetes (n=1) and pancreatitis (n=1). Of 84 irAE events, 47 (56%) have had complete resolution. Among all pts, 14.4% (n=45) required systemic steroids at any time (intravenous in 4.1%), 3.2% (n=10) require ongoing steroids/immunosuppression and 8.3% other therapy for an irAE (n=23 levothyroxine, n=1 hemodialysis, n=1 heart failure tx, n=1 insulin). Among all pts, 265 (85%) had an interim PET-CT after 2-4 cycles. The ORR and CRR at interim PET-CT were 97% and 78%, respectively. In the efficacy evaluable population (n=228), the EOT ORR and CRR were 96% and 90%. The median follow up was 10.2 mo (range 0.27-28.52). The 1-year PFS and OS estimates were 93.8% (95% CI: 90.8-98.4%) and 99.1% (95% CI: 97.9-100%), respectively. In multivariable analysis (MVA), only IPS score (OR 0.6, 95%CI: 0.59-0.60) was associated with lower CRR. In Cox univariable analysis, EBV+ status (HR=14.8, 95% CI: 3.2-69.2), IPS score (HR=1.5, 95% CI: 1.0-2.2), and ESR (HR=1.02, 95% CI: 1.00-1.04) were associated with worse PFS. Among the 11 pts with progression/relapse, 9 were primary refractory. 10 pts were started on second line (2L) therapy, and all pts are alive (1 pt pending 2L tx initiation). There were 2 deaths: one related to infectious complications and other unknown and both occurred after the first cycle of therapy. Conclusions: Pts treated with NAVD in a large RWS showed comparable response rates and 1-year survival outcomes to those in the pivotal S1826 trial. Most AEs were similar and grade 1-2, but close monitoring of irAEs is necessary given the potential long-term toxicity of checkpoint inhibitors and potential for ≥G3 irAEs (7.5%) in this young patient population. Our data supports the use of NAVD for 1L advanced stage cHL.

Abstract Background The benefit of high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a consolidation strategy after initial chemotherapy in peripheral T-cell lymphoma (PTCL) is currently unclear, and a randomized trial (EA4232/PTCL-STAT) to answer this question is currently underway. Angioimmunoblastic T-cell lymphoma (AITL) is a rare, aggressive subtype of nodal PTCL with poor prognosis and unique features. Here, we report a large-scale, real-world evidence on the role of ASCT in frontline AITL management. Methods We analyzed a national cohort of 5,827 patients diagnosed with AITL between 2004 and 2020 from the National Cancer Database (NCDB). Baseline demographic, clinical, and socioeconomic characteristics were assessed. Treatment modalities included chemotherapy alone, chemotherapy with ASCT, and no treatment. Overall survival (OS) was evaluated using Kaplan-Meier method and multivariable Cox proportional hazards regression. Propensity score matching (PSM) was performed to validate ASCT's treatment effect. Results Among patients with complete treatment information (n = 5,224), the median age at diagnosis was 68 years (range 20–90). Frontline treatments included chemotherapy alone (68.6%, n = 3,584), chemotherapy with ASCT (14.6%, n = 761), and no treatment (16.8%, n = 879). Compared with patients who did not receive ASCT, those who underwent ASCT were significantly younger (median 60.0 vs 68.0 years), more frequently treated at academic centers (81.5% vs 57.9%, p < 0.001), and more likely to reside in areas with higher educational attainment (p < 0.001). They exhibited lower Charlson-Deyo comorbidity scores (CDS), with a higher proportion having a score of 0 (82.8% vs 73.6%, p < 0.001), and were more likely to have advanced-stage disease (93.0% vs 86.9%, p < 0.001). Furthermore, a higher proportion of patients who received ASCT were diagnosed in more recent years (p < 0.001). Sex, race, and IPI score distribution showed no significant baseline differences. Median follow-up time was 81.1 months (95% CI: 77.4–84.9), and the median OS was 23.3 months (95% CI: 21.3–25.2) for the entire cohort. For patients receiving chemotherapy with ASCT, the median OS was 139.2 months (95% CI: 104.2–174.2). In comparison, chemotherapy alone yielded a median OS of 23.6 months (95% CI: 21.4–25.8), while patients who received no treatment had a median OS of 4.0 months (95% CI: 2.7–5.2); overall p < 0.001. Median OS also significantly improved with more recent diagnosis eras: 20.1 months for patients diagnosed in 2004–2009 (95% CI: 16.8–23.4), 23.9 months for those diagnosed in 2010–2015 (95% CI: 21.0–26.7), and 26.7 months for patients diagnosed in 2016–2020 (95% CI: 23.1–30.4) (p < 0.001). Analyses consistently demonstrated longer median OS in female patients (27.5 vs. 20.7 months in males, p <0.001), and in patients treated at academic centers (27.5 vs. 16.4 months at non-academic centers, p < 0.001). Median OS varied by race (White: 24.0 months vs. Black: 15.2 months vs. Others: 30.3 months; p = 0.017). Patients with higher household income and higher educational attainment experienced significantly improved survival (p = 0.005 and p = 0.017, respectively). Patients with early-stage disease, lower IPI scores, and lower CDS also showed significantly longer survival (p < 0.001 for all comparisons). Multivariate Cox regression showed that chemotherapy with ASCT significantly reduced mortality risk compared to chemotherapy alone (HR = 0.438, 95% CI: 0.364–0.527, p < 0.001). No treatment significantly increased mortality risk (HR = 1.941, 95% CI: 1.634–2.305, p < 0.001). PSM analysis further validated that chemotherapy with ASCT significantly lowered mortality risk compared to chemotherapy alone (HR = 0.608, 95% CI: 0.503–0.736, p < 0.001), after matching for age at diagnosis, sex, race, income, education level, academic center, stage, CDS, and diagnosis era. Conclusion This large-scale, real-world analysis suggests that chemotherapy followed by ASCT is associated with significantly improved overall survival in patients with AITL, supported by unadjusted Kaplan-Meier analysis, adjusted multivariate Cox regression, as well as PSM analysis. These data support ASCT as an important consolidation strategy for AITL in real-world practice.

Abstract Background Secondary central nervous system lymphoma (SCNSL) is a rare but significant complication, affecting approximately 2–10% of patients with diffuse large B-cell lymphoma (DLBCL), often leading to poor outcomes. The CNS-International Prognostic Index (CNS-IPI) remains a widely adopted tool for estimating CNS relapse risk; however, recent advances in molecular profiling and evolving treatment paradigms have challenged the adequacy of CNS-IPI alone in guiding risk assessment. This study evaluates the prognostic relevance of CNS-IPI in conjunction with molecular and clinical factors, specifically cell-of-origin (COO), gene expression, and frontline treatment regimens. The aim is to refine risk stratification and identify patients at highest risk for SCNSL. Method Building on our previous study, we analyzed data from patients with newly diagnosed DLBCL between 2002 and 2023, enrolled in the Mayo Clinic/University of Iowa Lymphoma Molecular Epidemiology Resource. Patients with primary CNS lymphoma, CNS involvement at diagnosis, or who received CNS-directed therapy were excluded. COO was determined using the Hans algorithm and/or Nanostring profiling. Multivariate cause-specific Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for predictors of CNS relapse that were measured at the time of initial DLBCL diagnosis. Cumulative incidence with competing risks and cause-specific Cox models were used to analyze relapse risk. Result We included 2137 patients in our analysis, median age at diagnosis was 63 (IQR 53-72), with 41.6% (n=890) females. The albumin level was below normal in 32.5% (n=350), 64.0% (n=1367) had CNS-IPI of intermediate/high, 37.5% (n=586) had non-germinal center B-cell (GCB) COO, and 14.5% (n=309) were double expressor positive. At a median follow-up of 83 months (IQR 42 -143), 82 (3.8%) SCNSL relapses were observed; the 3 and 5 yrs cumulative incidence for SCNSL from time of DLBCL diagnosis were 3.7% (95% CI 3.0-4.7) and 3.8% (95% CI 3.1-4.8) respectively. In models accounting for death as a competing risk, the 5-year cumulative SCNSL incidence estimate for patients with a CNS-IPI low was 1.5% (95% CI 0.8-2.7), Intermediate was 4.9% (95% CI 3.7-6.4), and high was 6.1% (95% CI 3.8-9.6). The 5-year cumulative SCNSL incidence estimate for patients with non-GCB COO was 5.2% (95% CI 3.6-7.4) compared to 2.4% (95% CI 1.6-3.6; p=0.001) for GCB patients, and the 5-year cumulative SCNSL incidence for double expressor positive patients was 8.6% (95% 5.8-12.6) compared to 1.5% (95% CI 0.8-2.7; p<0.001) for double expressor negative patients. In a multivariable model (including CNS-IPI, COO, double expressor, treatment group, extranodal involvement, and albumin group), CNS-IPI intermediate (HR 2.85 [1.58-5.14]; p<0.001) and high (HR 4.31 [2.15-8.65]; p<0.001), non-GCB COO (HR 2.36 [1.37-4.06]; p=0.002], double expressor (HR 5.56 [2.88-10.73]; p<0.001), and below normal albumin (HR 1.89 [1.02-3.50]; p=0.042) were independently associated with increased risk of SCNSL. The majority of the SCNSL relapse occurred within the first 2 years after DLBCL diagnosis; 81.7% (n=67), with only 6.1% (n=5) occurring after 5 years. For patients who developed SCNSL, the median OS from the time of SCNSL diagnosis was 24 months (95% CI 17-34), with 5 years OS of 31% (95% CI 22-43). These findings are being validated using an external, international cohort, and final analysis will be presented at the time of presentation at ASH. Conclusion In this large, prospectively followed cohort with long-term follow-up data, SCNSL remains a rare but devastating complication of DLBCL, with a 5-year cumulative incidence of 3.8% and it is associated with very poor long-term survival. While CNS-IPI remains a strong predictor of SCNSL risk, our study identifies non-GCB COO and double expressor phenotype as independent, additive molecular risk factors. These findings suggest that current risk stratification tools may underestimate the risk of CNS relapse in molecularly defined high-risk subgroups. Considering the poor outcomes linked to SCNSL and the absence of a connection with frontline treatment types, future research should aim to enhance risk prediction models through molecular profiling and explore prophylactic strategies to reduce the likelihood of SCNSL.

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.

e18017 Background: Head and neck (H&N) cancers affect the oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. In Sub-Saharan Africa (SSA), the true burden of H&N cancers remains unclear, with available estimates suggesting approximately 47,000 new cases and 26,000 deaths annually. Limited cancer datasets hinder understanding of disease patterns and outcomes. This study explores patient characteristics, treatments, and outcomes to guide regional cancer control efforts. Methods: A cancer dataset was created and implemented at 4 leading teaching hospitals in Ghana, Kenya, Ethiopia, and Rwanda to systematically collect data on patient demographics, disease characteristics, and treatment patterns. Established through competitive grant funding, the primary objective of the database was to assess the indirect impact of the COVID-19 pandemic on cancer care. The dataset includes all cancer patients seen in consultation and/or treated between 2016 and 2023. In this study, a subset of patients diagnosed with H&N cancers was analyzed using descriptive statistics to assess clinical characteristics, treatments modalities, and patients' outcomes. Results: A total of 1,023 patients with H&N cancer were included in the analysis. The median age at diagnosis was 54 yrs (IQR 41-66), with 37% (n= 374) of the cohort being female. A total of 55% (n= 549) had no health insurance coverage. Of those with staging data, majority presented with advanced disease (89%) on presentation. Regarding treatment modality, 16% (n= 157) underwent surgery, 27% (n=279) received radiotherapy (RT), 14% (n= 143) received chemotherapy (CT), and 56% (n= 572) received no cancer therapy. Of those who received CT the timing was neoadjuvant (12%), concurrent with RT (22%), adjuvant after surgery (8.9%) or as palliative treatment (57%). Platinum-based agents (94%) were the most common CT, followed by Taxol-based (31%), and 5FU-based agents (27%). Regarding RT, planning was performed using 2D (55%) and 3D (45%) techniques. The median delivered dose was 60 Gy in 30 fractions. At a median follow up of 43 months, 1.6% were disease free, 10% (n= 103) were alive, 5.9% (n= 60) were confirmed dead, and 84% (n= 848) were lost to follow up. Conclusions: This study identifies key challenges in managing H&N cancers in SSA, including late-stage presentation, limited access to advanced treatment modalities, and a high lost to follow-up rate (84%). The reliance on older RT techniques such as 2D planning and the limited use of surgery highlight gaps in infrastructure and resource availability. Limited health insurance coverage suggests potential financial barriers to care and disparities in treatment access. Addressing these challenges will require greater investment in cancer care, expansion of the oncology workforce, and improvements in healthcare infrastructure to support better patient outcomes in the region.

1510 Background: The National Comprehensive Cancer Network (NCCN) Harmonized Guidelines for Sub-Saharan Africa (SSA) have emerged as leading cancer treatment guidelines in SSA. The NCCN-SSA guidelines, derived by adapting NCCN guidelines for the SSA context, offer standardized recommendations to guide cancer care and shape policy in SSA. This study examines the evidence cited in support of the NCCN-SSA guidelines, with a focus on population characteristics and generalizability to SSA. Methods: Two reviewers independently examined the NCCN-SSA guidelines for the eight most common cancers in SSA to identify all studies cited in support of treatment/management recommendations. Study selection discrepancies were resolved by discussion. Full-text articles were reviewed and data on age, sex, race, and recruitment geography were abstracted. Descriptive analyses were performed using R statistical software. Results: Overall, 4,589 citations were reviewed, and 2,938 (64.0%) studies with individual-level data were included, representing >10.4 million study participants. Of the 2,061 studies reporting geographic information (70%), 50 (2.4%) recruited in SSA; of these, 39 (83.0%) recruited from South Africa. Three studies (0.2%) recruited exclusively in SSA. Most studies (95.3%) recruited exclusively from high or upper-middle income countries. Only 29.2% of studies with race data included >10% Black study participants. Conclusions: Most studies cited in the NCCN-SSA guidelines were conducted in high-income countries outside SSA. A small minority of all study participants were Black. Our findings underscore potential limitations in the generalizability of the NCCN-SSA guidelines to SSA and highlight a pressing need to generate and incorporate context-specific data to guide care and inform policy. WHO region of recruitment, race, and country-level income of studies included in NCCN-SSA guidelines. Cancer type # (%) studies reporting geography # (%) studies by recruitment region*: Americas # (%) studies by recruitment region*: Europe # (%) studies by recruitment region*: Sub-Sah. Africa % participants, White % participants, Black % participants, Other race # (%) studies representing only HMIC (per World Bank) Overall 2061(70%) 1177 (57%) 921 (45%) 50 (2%) 79% 9% 11% 1964(95%) B-cell 325(57%) 173 (53%) 178 (55%) 5(2%) 82% 7% 10% 307(94%) Breast 206(44%) 123 (60%) 124 (60%) 12 (6%) 80% 9% 11% 179(87%) Cervical 163(90%) 100 (61 %) 44(27%) 3(2%) 64% 14% 22% 158(97%) Colorectal 584(82%) 278 (48%) 292 (50%) 11 (2%) 80% 10% 10% 571 (98%) Hepato-cellular 183(74%) 80(44%) 68(37%) 0(0%) 69% 9% 22% 169(92 %) Kaposi sarcoma 51(80%) 25 (49%) 19(37%) 5(10%) 38% 51% 10% 44(86%) Ovarian 115(56%) 76 (66%) 35 (30%) 0(0%) 83% 4% 13% 115(100%) Prostate 434(88 %) 322 (74 %) 161 (37%) 14 (3%) 79% 9% 12% 421(97%) HMIC = high and upper-middle income countries. *Percent of studies includes as the denominator only the number of studies with reported geographies.

e17511 Background: Cervical cancer is a significant public health concern in Sub-Saharan Africa (SSA), where it remains the leading cause of cancer-related mortality among women. SSA has the highest global incidence and mortality rates, with an estimated 110,300 new cases and 76,700 deaths in 2020. Despite this burden, data on patient characteristics and treatment outcomes remain limited. This study aims to address these gaps by analyzing current treatment patterns and outcomes for cervical cancer in SSA. Methods: A cancer dataset was established at 4 major teaching hospitals in Ghana, Kenya, Ethiopia, and Rwanda to capture data on patient demographics, disease characteristics, and treatment modalities. The dataset encompasses all cancer patients seen between 2016-2023, with over 9,000 cases collected to date. The primary objective of the dataset was to assess impact of COVID-19 pandemic on cancer care in SSA. This study conducted a retrospective analysis of cervical cancer cases within the dataset utilizing descriptive metrics. Results: A total of 2,326 patients were analyzed, with a median age at diagnosis of 56 y (48–65) and 53% having health insurance. The majority had squamous cell carcinoma (87%) and presented with locally advanced disease (FIGO stages IIB–IVA, 88%). Treatment primarily consisted of concurrent chemoradiotherapy (CRT, 34%) or radiotherapy (RT) alone (30%), while smaller proportions received chemotherapy (CT) alone (1.2%) or surgery (1.3%). A total of 33% of patients received no cancer therapy. Among 1,524 patients treated with RT, 1,180 received external beam RT with a median dose of 46 Gy in 23 fractions, using 2D planning in 60% and 3D planning in 40% of cases. Additionally, 25 patients underwent brachytherapy, with 58% receiving low-dose-rate and 42% high-dose-rate treatments. Of 1,011 patients treated with CT, 85% (n=844) completed the intended course, with a median of 4 cycles, primarily delivered concurrently with RT (95%). Only a few received CT as adjuvant (4.8%), neoadjuvant (1.6%), or palliative (3.4%) therapy. Platinum-based regimens were most common, with 43% receiving platinum monotherapy and 5% receiving platinum-taxane combinations. By the end of treatment, 27% (n=633) achieved disease-free status. After a median follow-up of 47 months (range,37–55), 42% were alive, 7% had died, and 53% were lost to follow-up with unknown vital status. Conclusions: This study reveals significant challenges in management and follow-up of cervical cancer in SSA. Most patients were diagnosed at advanced stages, with 32% receiving no treatment and 53% of treated patients lost to follow-up. These findings highlight barriers to early diagnosis, treatment access, and continuity of care. Addressing these issues requires expanding early diagnostic services, increasing vaccination coverage, strengthening healthcare infrastructure, and improving patient retention.

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]

7052 Background: Secondary central nervous system lymphoma (SCNSL) is a rare but serious complication that occurs in 2-10% of patients (pts) with diffuse large B-cell lymphoma (DLBCL). The CNS-International Prognostic Index (CNS-IPI) is a validated tool used to assess the risk of CNS relapse. However, with advancements in molecular profiling and treatments, the predictors of SCNSL, including the predictive ability of CNS-IPI combined with other molecular markers and treatment regimens, have become uncertain. This study evaluates new prognostic markers for CNS relapse in DLBCL, focusing on cell-of-origin (COO), gene rearrangements, and treatment types. Methods: DLBCL pts enrolled from 2002-2015 in the Mayo Clinic and University of Iowa Lymphoma Molecular Epidemiology Resource were prospectively followed for incidence of CNS relapse. Pts with primary CNS lymphoma or CNS involvement at diagnosis, and pts treated with high-dose methotrexate containing regimens were excluded. COO classification (GCB vs non-GCB) was determined using Hans algorithm and/or NanoString data. Multivariate Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for predictors of SCNSL. Survival analysis was performed from time of DLBCL diagnosis using Cox proportional hazards model. Results: Among 1278 newly diagnosed DLBCL pts included (median age: 63 years; 43.6% female), SCNSL occurred in 46 (3.6%) pts. Pts with SCNSL were more likely to have intermediate/high CNS-IPI scores (80.4%) than pts without SCNSL (63.9%, p=0.02). The 3 yr SCNSL incidence was 0.016 (0.008-0.0033) in low CNS-IPI vs 0.043 (0.031-0.0060) in high CNS-IPI. Those with SCNSL were significantly more likely at baseline to have non-GCB COO (56.3% vs. 36.5%, p=0.02), and advanced stage (76.1% vs. 59.9%, p=0.03) compared to those without SCNSL. The incidence of SCNSL was not influenced by MYC, BCL2, or BCL6 rearrangements, nor by treatment with R-CHOP, R-EPOCH, or other immunochemotherapy regimens. MVA showed that intermediate CNS-IPI (HR 2.32, 95% CI 1.09-4.92, p=0.029), high CNS-IPI (HR 3.59, 95% CI 1.49-8.62, p=0.004), and non-GCB COO (HR 2.19, 95% CI 1.08-4.42, p=0.0029) were independently associated with increased SCNSL risk. After a median follow-up of 12 years (IQR 9–15), overall survival (OS) was 52.1% for the cohort, with OS significantly worse for SCNSL pts (17.4% vs. 53.4%, p<0.001). Conclusions: This large cohort with extensive follow-up highlights the role of COO as an additional prognostic factor for SCNSL while reinforcing CNS-IPI’s prognostic value. Non-GCB COO pts had a higher risk of SCNSL even when adjusted by CNS-IPI risk. Despite advancements in management, SCNSL pts continue to have poor outcomes. Strategies to reduce the incidence of CNS relapse in high-risk pts require further investigation. MER CNS relapse hazard ratios (95% CI). Characteristics Hazard Ratio 95% CI P-Value CNS-IPI Group 0-1 Low Ref Ref Ref 2-3 Intermediate 2.32 1.09 - 4.92 0.029 4+ High 3.59 1.49 - 8.62 0.004 Cell of Origin* GCB Ref Ref Ref non-GCB 2.19 1.08 - 4.42 0.029 Double Hit* non-DHL Ref Ref Ref DHL 1.08 0.14 - 8.3 0.941 Not Done/Missing 1.38 0.76 - 2.51 0.297 Double Expressor* Negative Ref Ref Ref Positive 2.36 0.71 - 7.85 0.162 Not Done/Missing 1.91 0.89 - 4.08 0.097 IC Group* R-CHOP R-EPOCH Ref 1.63 Ref 0.71 - 3.74 Ref 0.249 Other IC 1.18 0.57 - 2.46 0.660 Any EN Involvement* No Ref Ref Ref Yes 0.98 0.51 - 1.88 0.946 Albumin Group* >=Normal Ref Ref Ref <Normal 1.70 0.75 - 3.85 0.201 Head & Neck Involvement* No Ref Ref Ref Yes 0.35 0.048 - 2.63 0.310 *Adjusted by CNS-IPI risk group.