Purpose This study retrospectively reviewed the outcomes of patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab with bevacizumab (A + B) therapy at the Veterans Health Administration (VHA).Patients and Methods Patients with advanced HCC who received first-line systemic therapy with A + B at the VHA between December 1, 2019, and March 1, 2022, were selected from electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR of the patients from their index date of A + B initiation until death or their last VHA visit, with the study period ending on January 31, 2023. The chi-square test was used to compare rates, and the Mann-Whitney test was used to compare medians.Results A total of 332 patients met the study criteria. The median age was 67 years; 99% were male, 63% were non-Hispanic Whites, 26% were Black, and 66% had an Eastern Cooperative Oncology Group performance status of >= 1. 84% had child Pugh score (CPS) class A, 16% had CPS classes B and C, 62% had a grade 2 albumin-bilirubin score, 56% had HCC caused by viral hepatitis, 80% had cirrhosis, and 67% had received prior local therapies. The 6-month progression-free survival (PFS) was 59%, while the 1-year PFS rate was 36%. Overall survival (OS) at 1-year was 52% in our study.Conclusion In real world, despite having similar PFS as the phase III IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%) because our study included a higher proportion of elderly patients with moderate liver dysfunction and a 40% non-White. This study provided real-world outcomes that differed from the study population in a pivotal trial. This study retrospectively reviewed the outcomes of patients with advanced hepatocellular carcinoma receiving atezolizumab with bevacizumab (A + B) therapy at the Veterans Health Administration.

Abstract Drugs that disrupt the microtubule cytoskeleton, including both microtubule stabilizing taxanes and destabilizers like eribulin, are regularly used in the treatment of metastatic breast cancer. However, there are currently no molecular biomarkers to guide their use. Septins, a class of small GTPases, interact with both microtubules and actin to functionally link these cytoskeletal components and regulate cell biological processes shown to be critical for the invasion and migration of cancer cells. In particular, septin 9 (SEPT9) directly interacts directly with microtubules through an N-terminal domain on the longest isoform, SEPT9i1, which is sufficient to promote migration and invasion of breast cancer cells in vitro. We hypothesized that the relative expression of septin9 isoforms in breast tumors could play a role in their response to treatment with microtubule-targeted chemotherapy, particularly in the metastatic setting. A retrospective investigation of the relationship between septin expression and response to taxane chemotherapy was conducted utilizing full transcriptome sequencing data from biopsies of 75 breast cancer patients treated at our NCI-Designated Mays Cancer Center who received molecular profiling through Caris Life Sciences. Levels of total SEPT9 expression as well as the expression of specific variants that encode mechanistically distinct septin9 isoforms, SEPT9v1, v2, and v3, were determined for each sample and correlated with demographic, treatment, and outcome data for these patients. The oncogenic sept9_v1 variant (which produces the septin9_i1 isoform) was detected in over half of tumors and those with the highest total septin9 expression also expressed significantly higher levels of this isoform. Strikingly, the expression of total septin9, as well as the v3 variant, was significantly increased in taxane-treated patients who survived over a year after diagnosis with metastatic breast cancer, suggesting that septin9 expression could be a molecular correlate of response to taxane chemotherapy. We found that the expression of total septin9 and its variants was not significantly correlated with race, ethnicity, or cancer type suggesting that our findings would apply to our patient population as a whole, which is over 50% Hispanic. These data were used to support an ongoing prospective study to determine effect of septin expression on response to taxane chemotherapy in the neoadjuvant setting and determine the effect of taxane treatment on septin expression by comparing samples pre and post treatment. Together this work supports our overall goal of identifying predictive biomarkers to facilitate the use of microtubule targeted chemotherapy in a more personalized manner. Citation Format: Tamarah Aldawoodi, Jacob Nathaniel Essif, Amna Naqvi, Lauren D. Boyle, Daniela Urueta Portillo, Kate Lathrop, April L. Risinger. Determining the role of septin expression in response of breast cancer patients to microtubule targeted chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5163.

4109 Background: The incidence and mortality of HCC are increasing in the USA. HCC disparities have been reported across the entirety of the cancer timeline, from screening to local and systemic treatment and liver transplant. We aim to analyze the clinical characteristics, outcomes, and racial disparities in patients with advanced HCC receiving first-line Atezolizumab plus Bevacizumab (A+B) in the Veterans Health Administration (VHA) – the only health care system in the USA that provides equal access to all patients. Methods: Patients were followed from their A+B initiation date through the earliest of the last VHA visit, loss to follow-up, death, or end of study on Jan 31, 2023. Structured electronic health record and chart review data were retrospectively collected to determine patient baseline characteristics, including self-reported race, number of A+B doses, treatment response, subsequent line of treatment, length of follow-up, and overall survival (OS). The Chi-Squared test was used to compare rates, and Mann-Whitney test was used to compare medians. Results: Three hundred twenty-five patients were included. 64% were non-Hispanic White (NHW), and 36% were all other (AO) ethnicities or races combined (26% Black, 8% Hispanic, 2% Asian or Indigenous). The median age for each cohort was similar (66 years for AO vs. 68 for NHW), and ECOG performance was <1 in nearly 90% of each cohort. Viral hepatitis accounted for 70% and 48% of AO and NHW, respectively (p=0.0001). Despite clinical differences in OS and progression free survival (PFS), they were not statistically significant. Conclusions: Our VHA real-world data shows that despite having statistically significant etiologies, there was no statistically significant difference in the PFS and OS of patients with advanced HCC receiving first-line A+B in an equal access care system. This study supports our group’s findings in other malignant cohorts within VHA where equal healthcare access can mitigate other socio-demographic and biological factors. [Table: see text]

e16195 Background: Atezolizumab plus Bevacizumab (A+B) has been the standard first-line therapy for advanced hepatocellular carcinoma (HCC) patients. There needs to be more data on the efficacy and selection of optimal sequences following resistance to A+B. Our study aims to review treatment patterns for disease progression following A+B, focusing on the most common 2nd line treatment utilized by the Veterans Health Administration (VHA). Methods: Patients with advanced HCC receiving line A+B at the VHA between Dec 1, 2019, to Mar 1, 2022, were selected electronically using ICD-9 and ICD-10 codes. Abstractors reviewed EMR following each patient from their index date of A+B initiation, sequential therapies, until death, or their last VHA visit, with the study period ending on Jan 31, 2023. Results: Three hundred thirty-two patients received A+B during our study period, and 1/3rd (n = 107) of these patients went on second-line treatments. 87 % started Tyrosine Kinase Inhibitors with 52, 29,12, and 1 on Lenvatinib, Sorafenib, Cabozantinib, and Regorafenib, respectively. Two second-line cohorts were selected, A (52 on Lenvatinib) and B (29 on sorafenib). The median age was 66 yrs vs. 65 yrs in cohorts A and B, respectively. In both cohorts, 60% non-Hispanic White and 90% with ECOG ≤1, there were no statistically significant differences between both cohorts in overall and progression-free survival. The outcomes are shown. Conclusions: Despite minimal improvement in PFS and a lower discontinuation rate due to toxicity favoring Lenvatinib over Sorafenib, Sorafenib had slightly better overall survival. This study is one of the most significant projects that describes 2nd line treatment patterns post-A+B failure. Further studies are warranted to evaluate larger cohorts to study treatment sequencing in the second and third lines.[Table: see text]

e16129 Background: Treatment options for aHCC have drastically improved over the past few years with immunotherapy at the forefront. Ongoing studies aim to identify the benefit of immunotherapy in combination with local therapies, but there are no studies that analyze the impact of previous local therapy on OS in patients who later receive A+B for treatment of aHCC. This study aims to analyze the impact of previous local therapy on OS in patients with aHCC treated with first line A+B within the Veterans Health Administration (VHA). Methods: Patients with aHCC receiving first line systemic therapy with A+B at VHA between Dec 1, 2019 through Mar 1, 2022 were identified from the electronic medical record (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR and followed the patients from the date of diagnosis, date of local treatment and date of A+ B initiation until death or their last VHA visit with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates and the Mann-Whitney test was used to compare medians. Results: 332 patients with aHCC received A+B. 67% of patients received prior LT. Patients who received LT had better ECOG status, Child-Pugh classification, and BCLC staging at time of diagnosis. There was no difference in age at diagnosis, race/ethnicity, ALBI score at time of diagnosis or at time of starting A+B, or presence of extrahepatic spread at time of starting A+B. There was a statistically significant difference in time from HCC diagnosis to start of A+B, with patients who received LT having a longer interval time. There was a small but not statistically significant difference in median OS from the start of A+B, favoring people who received LT. Conclusions: Our unique retrospective study confirms that patients receiving LT have better OS from the time of diagnosis. Disease biology and LT response may be contributing to this survival benefit. However, the OS was similar from the time of initiation of A+B in patients receiving LT versus patients who did not receive any LT.[Table: see text]

CONCLUSION High grade lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (HGL) occur in less than 10% of DLBCL. While clinical trials demonstrated poor outcomes following standard rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) therapy for HGL since the early 2000s, the World Health Organization (WHO) identified this as a new category in 2016. There was a lack of consensus for FISH testing until NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) (V.1.2020) moved Karyotype/FISH testing for MYC from “USEFUL UNDER CERTAIN CIRCUMSTANCES” to “ESSENTIAL”. NCCN Guidelines ® V.1.2018 recognizes the lack of standard of care for HGL and comments about using dose-adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) DA-EPOCH-R for this category. The VHA is the largest integrated, uniform care access system in the United States. The objective of this study is to understand the real-world applications of NCCN Guidelines on testing and treatment patterns in DLBCL within VHA. 6266 patients were randomly selected for this retrospective chart review with an ICD code for DLBCL managed in the VHA from 01/01/2011 to 12/31/2021. This 11-year period is divided into three blocks: 2011-2015, 2016-2019 and 2020-2021, which represent pre-identification of HGL based on WHO classification, post-identification of HGL based on 2016 WHO classification Lymphoid neoplasm classification, and the change in MYC testing NCCN Guidelines(Version 1.2020), respectively. VHA is divided into five geographic regions, which includes the Pacific, Continental, Midwest, Southeast, and North Atlantic. Data abstractors collected baseline patient and disease characteristics, both manually and electronically, including but not limited to, testing and treatment patterns for those with a diagnosis of DLBCL in each time frame. Statistical comparisons were done using the Chi-Squared test. 3178 met our inclusion criteria for DLBCL. Of the total patients, 1471 (46.3%) had FISH testing performed. Table 1 shows baseline characteristics. Of the patients tested, 97% of the patients were male, 75% were non-Hispanic white and median age was 68 years. The median Charlson Comorbidity Index (CCI) was 2. FISH testing rates increased over time from 28% in the first study period to 76% during the last study period. There was no statistically significant racial difference in FISH testing rates. Continental VHA district patients were less likely to have FISH testing completed when compared to other districts (p<0.0001). Despite an overall increase in FISH testing, as well as a change in testing NCCN Guidelines(Version 1.2020) there was no significant increase in the real-world utilization rate of DA-EPOCH-R for HGL during the different study periods (Figure 2). This is one of the largest retrospective studies reporting FISH testing and treatment patterns based on NCCN Guidelines for HGL. Despite significant improvement in the rates of FISH testing during our study period, there are significant regional differences, and 25% of the patents did not undergo FISH testing after the recommendation change in 2020. Our data also highlights the underutilization of DA-EPOCH-R in HGL patients within VHA. This may be attributed to knowledge gaps, diagnosis at older age, higher Charlson score due to multiple comorbidities, and regimen feasibility. Limitations of this study include a predominantly older, male population with equal health care access that may limit generalizability of our findings to the non-Veteran population. Data from our study underscores a need for increased awareness of NCCN Guidelinesrecommendations both in terms of testing and treatment planning outside the clinical trial setting.

Introduction The median age for DLBCL diagnosis is 66 years. Incidence increases with age and about 30% of patients diagnosed are over 75 years old. In the context of an aging population, unfit or frail individuals pose a unique challenge due to their limited tolerance for combination chemotherapy and are often excluded from clinical trials. The VHA is one of the largest integrated providers of cancer care in the United States catering to an older population, making it ideal to study real-world outcomes in this geriatric population. This study presents the final analysis of our large cohort of geriatric patients (≥ 65 years old) diagnosed with DLBCL treated within the VHA. Methods This study reviewed 6266 randomly selected patients with an ICD code for DLBCL within the VHA between January 1, 2011, and December 31, 2021. Patients were excluded if they had a diagnosis other than DLBCL, incomplete records, or diagnosed and/or treated outside of the VHA. Data abstractors collected baseline patient and disease characteristics and treatment responses. Fall and delirium rates,Charlson Comorbidity Index and survival rates were determined via electronic health record query. Patient population ≥ 65 years old were divided into three age groups: 65 to 74 years, 75 to 84 years, and ≥ 85 years, represented by A, B, and C, respectively. Chi-square tests were used to analyze the relationship between age and variables of interest. Results Of the total population 3178, 2124 (66.8%) qualified for data analysis due to the age cut of ≥ 65 years. The distribution of age was 61.0%, 28.8%, and 10.2% in A, B, and C, respectively. The demographics and clinical characteristics of the patients are shown in Table 1. 18.3% of patients in C had an ECOG score 3-4 compared to 16.4% in B and 9.0% in A. With increasing age, patients had an increased incidence of repeated falls and delirium within the six months prior to and following diagnosis (5.9% in A vs 8.0% in B vs 10.1% in C). Across all age groups, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remained the most common first-line regimen. The utilization of R-CHOP decreased significantly from A to C (69.7% vs 53.5% vs 27.5% in A, B, and C, respectively). In comparison to the other age groups, patients in group C were more likely to receive R-mini-CHOP (1.5% in A vs 9.8% in B vs 19.7% in C). As shown in Figure 1, the percentage of patients that did not receive any chemotherapy increased with age (5.3% vs 11.8% vs 30.7% in A, B, and C, respectively, p=<0.001). Of those who received chemotherapy, 23.2% in A, 32.7% in B, and 39.7% in C did not complete the intended number of treatment cycles. 693 (32.6%) patients did not receive any treatment or were not able to complete the intended number of cycles. Among patients who received treatment, older patients were more likely to have primary refractory disease or die before completing the first line of treatment (21.8% vs 24.4% vs 34.8% for A, B, and C, respectively, p=0.001). Additionally, geriatric patients with primary refractory disease were less likely to receive salvage therapy. Median overall survival was 71, 42, and 14 months in A, B, and C, respectively. The 12-month survival rate was 77% in A, 69% in B, and 51% in C. Only 1.3% of the total population were enrolled in a clinical trial. Conclusion This study is one of the largest to examine disease patterns, treatment approaches, and outcomes in a geriatric cohort diagnosed with DLBCL within the VHA. Low treatment initiation and completion rates decline significantly with age above 65 years. Poor performance status and increased incidence of delirium and falls lead to a low percentage of very elderly patients completing the intended number of chemotherapy cycles. Our study suggests that approximately one-third of patients are unable to receive first line treatment or are unable to complete first line intended treatment. The outcomes are dismal for patients with relapse or refractory disease which further contributes to very low long-term survivals. Novel therapies, such as antibody drug conjugates, bispecific T-cell engagers and chimeric antigen receptor T-cell therapy offer different toxicity profiles and possible increased tolerance. Nonchemotherapy-based novel agents in upfront approaches should include geriatric patients in clinical trials to ensure that the benefits of medical advancements extend to this population addressing the unique challenges they face.

INTRODUCTION: The incidence of DLBCL in the United Sates is projected to increase to 32, 443 new cases per year by 2025. With increasing incidence and prevalence, DLBCL prognosis has improved significantly in the past decade through the addition of novel therapies such as new monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) therapy, antibody-drug conjugates, and most recently bispecific T-cell engagers. Despite these improvements, racial and ethnic disparities continue to impact outcomes in DLBCL patients (Flowers 2012). The purpose of this study was to assess racial and ethnic differences in DLBCL patients and outcomes within the VHA, an equal access system where confounding factors such as disease biology and socioeconomic status are more controlled giving us an opportunity to examine racial disparities. The aim of this study is to present a final analysis the final analysis of racial and ethnic differences in DLBCL patients within the VHA over a time span of 11 years. METHODS: Trained abstractors performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. Patients diagnosed with DLBCL were included. Patients were excluded if they had a diagnosis other than DLBCL, had incomplete records, or were diagnosed and treated outside the VHA. Data was collected on baseline patient demographics, disease characteristics, and treatment. Survival time was determined via electronic health record query on 1/4/2023. The study population was divided into non-Hispanic Black (NHB), non-Hispanic White (NHW), Hispanic (H), and other. Chi-squared tests were used to analyze the relationship between race and variables of interest. RESULTS: 3178 patients met inclusion criteria for analysis. Patients were predominantly male with a median age of 69 and presented primarily with advanced disease (Baseline Characteristics-Table 1). NHB were diagnosed at a younger median age (63 years) when compared to the NHW, H and other (69 years, P < 0.001). Patients in each subgroup presented with similar rates of stage I/II and III/IV disease with no statistically significant difference in stage at presentation amongst each racial subgroup (P=0.61). Of all the patients who received chemotherapy, the objective response (OR) rate was 79.2% with a complete response (CR) rate of 66.4%. The response rates were similar across the 4 subgroups with most patients achieving a CR after first-line therapy (P=0.74). There were no statistically significant differences in OR rates amongst subgroups (P = 0.95). Median overall survival (mOS) for the entire population was 69.6 months (95% CI = 65-75), with a mOS of 85.1 months (67-112), 85.9 months (60-112), 67.4 months (60-73), and 71.2 months (49-122) for NHB, H, NHW, and other patients respectively (Figure 1). There was no statistically significant difference in mOS amongst subgroups (P = 0.13). The 1-year, 3-year, and 5-year survival rates were also similar between subgroups (P=0.97, P= 0.39, P=0.32 respectively). CONCLUSION: This study represents one of the largest retrospective analyses of DLBCL in the VHA nationwide, highlighting that there is no statistically significant racial difference in DLBCL outcomes for patients treated within the VHA. Our study highlights the significance of equal access system and that disease biology and other social factors can be mitigated resulting in equal response to treatment and OS amongst all groups. Potential limitations of this study include using retrospective data on a predominantly white, male population that may not truly represent general DLBCL population data. The study period is mainly until 2021 with limited data on the accessibility of newer, novel treatments. With the development of newer, expensive treatments, especially Bispecific T Cell Engagers and CAR-T therapy, it is imperative to study utilizations of these novel treatments and study racial differences in this new treatment non-chemotherapy-based era.

Introduction Around 30%-40% of patients with diffuse large B-cell lymphoma (DLBCL) will experience disease progression or relapse after first line (1L) chemoimmunotherapy with most patients relapsing within the first 12 months. Relapse may be systemic, isolated to the central nervous system (CNS), or both with CNS relapse occurring in 2-5% of patients. The purpose of this study is to evaluate the characteristics and outcome differences of Veterans diagnosed with DLBCL within the VHA who experienced systemic relapse, isolated CNS relapse or both. Methods A retrospective chart review of 6,266 lymphoma patients seen in the VHA nationwide between 01/01/2011 and 12/31/2021 was performed by trained abstractors. Patients diagnosed with DLBCL were included. Patients were excluded if they had a diagnosis other than DLBCL, had incomplete records or were diagnosed and treated outside the VHA, had baseline CNS involvement, did not receive treatment, or died before receiving a scan to assess response to 1L therapy. Outcomes including response to 1L treatment, time to relapse and overall survival (OS) defined as time from diagnosis to death were evaluated. Early relapse was defined as having primary refractory disease (stable or progressive disease (SD or PD) as best response to 1L therapy) or disease progression in ≤12 months in patients achieving a complete response (CR) or partial response (PR). Late relapse was defined as disease progression >12 months. Results A total of 2,658 patients met inclusion criteria for analysis with 97% of the population being male, 65% with stage III-IV disease, and 90% with an ECOG performance status of 0-2. Of the total cohort, 74% of patients received a CHOP-based regimen, 74% had an intermediate- or high-risk CNS International Prognostic Index (CNS-IPI) score, 81% did not receive a baseline diagnostic lumbar puncture (LP) and 86% did not receive any CNS prophylaxis. The median follow-up time for subjects in this study was 54 months. Relapse occurred in 29% of the total cohort with systemic only relapse occurring in 27% of patients, isolated CNS in 1%, and CNS + systemic in 1%. Of the 761 patients who experienced relapse, 77% had an early relapse with a median time to relapse of 4.4 months (IQR 2.8-6.7). For the 23% of patients with late relapse, the median time to relapse was 25 months (IQR 18-41). The characteristics of patients who experienced relapse were similar regardless of type of relapse or time to relapse (table 1). A higher percentage of patients with early relapse had a high-risk CNS-IPI score, bone marrow involvement, and renal or adrenal involvement. Autologous stem cell transplant was performed in 11% of patients, predominately in those with systemic only relapse. The median OS (mOS) was similar between relapse types with systemic, isolated CNS, and CNS + systemic having a mOS of 23.5 months (95% CI: 21-27), 30.6 months (95% CI: 15-71), and 29.6 months (95% CI: 20-45), respectively (p=0.75). Figure 1 describes mOS by relapse type and time to relapse. Overall, patients with early relapse had a poorer prognosis regardless of relapse type with a mOS of 17 months (95% CI: 15-18) compared to a mOS of 68 months (95% CI: 59-88) in patients with late relapse (p<0.001). The 24-month survival rate of those with early versus late relapse was 37% and 78%, respectively. Patients with a late systemic relapse had the longest mOS of 74 months (95% CI: 60-90). Conclusion This is the largest study reporting outcomes of Veterans who experienced relapsed DLBCL within the VHA. Although earlier data suggests specific features may correlate with early versus late relapse, all characteristics were similar in our population across relapse types regardless of time to relapse. The rate of relapse in the total cohort and the rates of CNS relapse were lower than previously reported, adding to recent data suggesting the use of CNS prophylaxis may have limited benefit. Patients with early relapse performed poorly and may benefit from novel therapies including chimeric antigen receptor T-cell therapy, which could not be evaluated with this study. The retrospective nature of this analysis, and a predominately male veteran population may limit external application.

Background: Primary Mediastinal B-cell Lymphoma (PMBL) is a rare, aggressive Non-Hodgkin Lymphoma (NHL) accounting for approximately 2-5% of all NHL (PMID: 34330673). Due to its rarity, there is scarce literature on the demographic features of PMBL. Moreover, there is little to no research on outcomes of ethnic minority groups, particularly in Hispanics (HI) (PMID: 27399089.) Thus, there is a need for further investigation of disease characteristics to advance treatment options for the future. This is a national scale population-based analysis examining disparities in HI vs Non-Hispanics (NH) and its impact on survival outcomes in patients with PMBL. Material and Methods: Data was analyzed on PBML patients in the United States reported to the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. SEER contains the most comprehensive population-based cancer information in the U.S., covering approximately 27% of the total US population, and up to 36% of Hispanics alone. Racial groups analyzed included non-Hispanic whites, Hispanic whites, blacks, and Asians/PIs (Pacific Islanders). Patient characteristics, age-adjusted incidence rate, and survival rate were compared across ethnic groups, Hispanics (HI) vs Non-Hispanics (NH). Stratification by age, gender, and stage at diagnosis was considered. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH. Multivariate analysis and propensity score matching were performed with adjustment for age, stage and B-symptoms. Results: Of 1,014 PMBL patients, 15% were HI, and 85% were NH. PMBL affects mostly women in both HI and NH (66% and 60% p=0.215). HI were diagnosed at a younger median age, 30 y.o vs 36 y.o (p=0.001), compared to NH. The majority of HI and NH were diagnosed under 40 years old (p=0.010). Both groups were mostly diagnosed between 2015-2018 (44% vs 41%) (p=0.768). The majority of both groups did not receive radiation, however it was noted that HI received less radiation compared to NH (72% vs 66%) (p=0.180). The median survival time was not reached indicating a favorable prognosis. On survival analysis; the survival probability of HI vs NH at 2 years was 0.87 vs 0.86, at 5 years 0.85 vs 0.85, and 10 years 0.83 vs 0.82. and there was not an OS difference favoring HI/NH (p = 0.94). On multivariate analysis, when adjusting for age, those who were older than 80 y.o and between 60 to 80 y.o, had worse OS compared to those younger than 60 y.o with HR 9.3 (95% CI: 4.3 - 20) and 8.8 (95% CI: 4 - 19). Conclusions: Our study analysis shows that the demographic variables between HI and NH were generally homogenous. In patients with PMBL, HI were diagnosed younger compared to their NH counterparts, however this did not affect OS. In conclusion, HI and NH patients with PMBL had similar treatment and outcomes showing that, when there is equity in health, favorable prognosis is possible with the current standard of care. Citation Format: Lauren Diaz Boyle, Esteban Toro-Velez, Adolfo Enrique Diaz Duque. Population-based analysis of primary mediastinal B-cell lymphoma: a look at Hispanic outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1913.

2651 Background: Advanced Hepatocellular carcinoma (HCC) is an aggressive tumor, and most patients have a poor prognosis. Recent clinical trials have demonstrated improved survival with molecularly targeted treatment and immunotherapy. Atezolizumab plus Bevacizumab (A+B ) is the recommended first-line treatment for advanced HCC based on the phase 3 IMbrave 150 trial. However, in a real-life setting, many patients do not meet the inclusion criteria of this landmark trial. This study proposes a retrospective review of outcomes of advanced HCC patients receiving A + B in Veterans Health Administration (VHA). Methods: Patients with advanced HCC receiving 1st line systemic therapy with A+ B at the VHA between Dec 1, 2019, to Mar 1, 2022, were selected from the electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed EMR and followed from their index date of A+ B initiation until death or their last VHA visit, with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates, and the Mann-Whitney test was used to compare medians. Results: A total of 332 patients met the study criteria. The median age was 67 yrs., 99% were males, 63% non-Hispanic White, 26% were Black, 66 % had ECOG ≥ 1, 84% had CPS class A, 16% had CPS class B and C, 62% had grade 2 ALBI score, 56% had viral hepatitis-caused HCC, 80 % had cirrhosis, and 67% had prior local therapies. The outcomes are shown. Conclusions: In our real world, despite having similar PFS as the phase 3 IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%), given that we had more elderly patients with moderate liver dysfunction and 40% were non-white. This study provides actual outcomes in clinical practice where patients do not match the study population of the pivotal trial. [Table: see text]

Introduction: The standard treatment approach for DLBCL has traditionally relied on chemo-immunotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) for decades. However, approximately 30-40%, remain refractory or experience relapse with poor outcomes. Since 2017, the landscape for relapsed refractory DLBCL has changed dramatically with the FDA approval of newer monoclonal antibody, chimeric antigen receptor (CAR) T-cell, antibody-drug conjugate, and bispecific T-cell engagers. Nonetheless, a comprehensive analysis of population survival outcomes since the new treatment modalities remains to be evaluated. In this study, we present an extensive demographic analysis of one of the largest DLBCL cohort to date within the VHA, spanning over 11 years, and the survival outcomes before and after 2017 period. By assessing this vast dataset, we aim to provide valuable insights into the changing landscape of DLBCL treatment and its impact on patient survival. Methods: Using the VHA electronic database, 6266 patients with an ICD code for DLBCL were randomly selected for this retrospective chart review from 01/01/2011, to 12/31/2021. Diagnosis outside of these dates or lack of any treatment history were excluded from the study. Patients were separated based on the diagnosis date into pre- and post-2017 era, diagnosis prior to 1/1/2017 vs diagnosis on and after 1/1/2017. Baseline disease characteristics, treatment patterns and outcomes were collected manually by trained abstractors. Finally, we calculated the overall survival (OS) and graphed using Kaplan Meier method comparing the pre- and post-2017 era. P-values were calculated using Log-Rank test or Chi-Square test. Results: 2660 patients were included in the final analysis. Baseline characteristics between the two groups were comparable. Of all patients, 73% achieved complete response (CR) to the first-line treatment. Most of the patients (1968 patients, 74%) received CHOP-based therapy as their first-line regimen with a median of 6 cycles, and this did not differ significantly between the pre- and post-2017 era. Diagnostic lumbar puncture was performed in 19% of all patients, and about 14% of the patients received CNS prophylaxis. Only 4.2% of all patients proceeded with hematopoietic stem cell transplantation (HSCT). Notably, patients diagnosed post-2017 had fewer HSCT than pre-2017, 2.7% vs 5.1% respectively. The median overall survival of all patients in the pre-2017 group was 96 months whereas post-2017 was not reached yet (P-value 0.011). Further analyzing the outcomes of the veterans who experienced refractory or relapsed disease, based on the date refractory or relapsed disease diagnosis, we identified improved OS for an extended period in the post-2017 group. The median OS of pre-2017 was 21 months vs post-2017 was 28 months (P-value 0.013). The OS rate at 12 months and 60 months was 66% vs 76% (P-value 0.003) and 25% vs 32% (P-value 0.034) in the pre-2017 and post 2017 era respectively. However, the OS rate at 96 months was 17% vs 19% was not different statistically (P-value 0.48). Conclusions: This is the most extensive DLBCL population-based data set existing, encompassing survival outcomes over a decade. Our study shows improved OS in patients diagnosed with refractory and relapsed disease on 1/1/2017 and beyond compared to the pre-2017 era, highlighting the available newer treatments outside the rituximab-based chemo-immunotherapy and refined supportive care. The improved survival extends to over 5 years. However, the overall survival remains similar after 8 years, irrespective of treatment era. This finding suggests that other factors, such as comorbidities, appear to play a role in mortality, rather than the disease itself or its treatment. The limitation of the study includes limited follow up period for patients diagnosed post 2017 era and the predominantly male population found in the VHA system, which represents a restricted view of a real-world population.

4107 Background: Most clinical trials use Child-Pugh (CP) for patient selection; this subjective scale was originally developed to assess liver function in cirrhosis, thus cannot be applied to HCC patients with non-cirrhotic background. Alternatively, ALBI grade is an objective and validated prognostic system that has demonstrated improved accuracy to predict survival and liver function decline in HCC patients. Our real-world study aims to assess the ALBI grade as a predictive marker of treatment response in patients with advanced HCC who received (A+B) within the VHA. Methods: VHA patients with HCC receiving 1st line therapy with A+B were identified through EMR using ICD-9 or ICD-10 codes between 1 Jan 2007 and 31 Dec 2021. Patients were followed from their A+B initiation date through the earliest of the last VHA visit, loss to follow up, death, or end of study on Jan 31, 2023. Structured electronic health record and chart review data were retrospectively collected to determine patient baseline characteristics, treatment response, overall survival (OS), and progression-free survival. Survival rates were based on patients with at least 6 months or 1 year of time (as indicated) from A+B initiation until the chart was reviewed; patients without a scan or known date of scan were excluded from PFS calculations. The Chi-Squared test was used to compare rates. Results: 332 patients were included in the study. The median age was 67 yrs, 99% were males, 63% non-Hispanic White, 26% Black, 86% with ECOG < 1, 84% had CPS class A, 16% had CPS class B and C, 56% had viral hepatitis-caused HCC, 20% had no cirrhosis present, and 60% had prior local therapies. There was a statistically significant difference in progression free survival (PFS) and over survival (OS) amongst different ALBI grades as shown. Conclusions: In our retrospective cohort, it was clear that patients with ALBI grade 1 had improved PFS and OS compared to ALBI score grade 3. Patients with ALBI score grade 2 also had a moderate response to treatment with modest OS and PFS compared to patients with ALBI score grade 3. Utilizing stratification ability ALBI grade in future clinical trials may improve prognostic power facilitating ideal patient selection. [Table: see text]

e24022 Background: Over the last decade, the incidence of Hepatocellular carcinoma (HCC) has increased in the geriatric population. Atezolizumab plus Bevacizumab (A+B) has become an established systemic therapy for patients with HCC. Even with the aging population and elevated prevalence of HCC amongst Veterans, limited studies have explored the safety of A+B in geriatric patients. This study aims to investigate the toxicity profile of A+B in the geriatric population as well as Palliative Care and Hospice utilization within the Veteran Health Administration (VHA). Methods: Data were extracted from the electronic medical records (EMR) for adults (deceased and living) with ICD9 and ICD10 HCC codes that received 1st line systemic therapy with A+B within the VHA between December 1, 2019, and March 1, 2023. Descriptive statistics were used to summarize baseline characteristics, toxicity profile and Palliative Care and Hospice enrollment between 3 populations aged < 65, 65-69, and > 70 years. A significant p-value of ≤0.05 was used. Results: In total, 332 patients were included in the study; 206 were deceased. Approximately 70% of patients were > 65 years. The majority in each age group were non-Hispanic white males, ECOG ≥1, CPS class A and BCLC score of C. Veterans > 70, significantly had less cirrhosis caused by viral hepatitis(p < 0.0001) and no prior local therapy (p = 0.002). There was no significant difference in either median A+B doses, cessation of therapy due to toxicities or median reported toxicities of any grade, as reported in Table 1. Most common toxicities in all age groups were fatigue, decreased appetite, proteinuria and transaminitis. There was a significant difference in Hospice enrollment in deceased patients (p = 0.027), with Veterans > 70 years more likely to enroll in Hospice. Conclusions: This is the first known study that reports geriatric advanced HCC patients with A+Z toxicities in VHA patients. This study demonstrates that A+Z can be used safely in geriatric patients. Further quality improvements projects need to be implemented to improve number and timing Hospice utilization.[Table: see text]

INTRODUCTION:Our retrospective study evaluates the impact of time from diagnosis to treatment (TDT) on outcomes of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated within the Veterans Health Administration (VHA).METHODS:VHA patients diagnosed with DLBCL between 2011 and 2019 were included, while those with primary central nervous system lymphoma were excluded. The median overall survival and progression-free survival were estimated with the Kaplan-Meier method. Univariate, bivariate, and multivariable analyses were performed using the Cox proportional hazards model. The odds ratio for refractory outcomes was calculated using logistic regression.RESULTS:A total of 2448 patients were included. The median time from diagnosis to treatment of the cohort was 19 days. When comparing median progression-free survival, median overall survival, and the 2-year overall survival between the group that started treatment within 1 week and each of the other groups individually, there was a significant difference favoring improved survival in all groups with a TDT longer than 1 week (P < .0001). These patients also had a lower odds ratio for refractory outcomes. On multivariable analysis, TDT remained an independent prognostic factor.CONCLUSION:Our study shows that a TDT equal to or less than 1 week is associated with adverse clinical factors, worse outcomes, and response in DLBCL, even after adjusting for multiple known poor prognostic factors. This was the first time that response to first-line therapy was correlated to time to treatment. Our findings support ongoing efforts to improve currently standardized prognostic tools and the incorporation of TDT into clinical trials to avoid selection bias.

Introduction: Even in the Rituxan era, patients with primary refractory or relapsed LBCL have poor outcomes. The standard of care for these patients is salvage therapy (ST) as second-line treatment followed by high dose therapy with autologous stem cell transplant (ASCT) in chemosensitive patients with an estimated 30-40% of ST responders deemed eligible to undergo transplant (PMID: 28774879). Currently, chimeric antigen receptor (CAR) T-cell therapy is the standard of care for high risk LBCL (high International Prognostic Index (IPI), HIT status) who do not respond to ST and have manageable safety profiles and high efficacy. Promising CAR T data is also emerging for early chemotherapy failure and as alternative second-line therapy (PMID: 35314842). The purpose of this study is to analyze the treatment patterns and survival outcomes of primary refractory and relapsed population of LBCL within the VHA. Methods: This is a retrospective chart review of 5199 randomly selected patients with an ICD code for lymphoma treated within the VHA between 01/01/2011 and 12/31/2019. Data abstractors included patients with LBCL who completed first-line chemotherapy treatment and had documented post-treatment scans (PET, CT). We defined primary refractory as either stable disease (SD) or progressive disease (PD) based on post-treatment scans and relapsed disease as recurrence of disease within 12 months of post treatment scans. Median overall survival (OS) was calculated using the Wilcoxon-Mann-Whitney test. Results: A total of 2288 patients met inclusion criteria who received or completed treatment at the VHA. Baseline characteristics are outlined in Table 1. From our analysis, 299 (13.1%) of patients were primary refractory. Median age was 68.9 years and 97% were male. European Cooperative Oncology Group (ECOG) was 0-2 (81.3%). Stage at diagnosis was III-IV (83.9%). Most patients had an IPI score ≥3 (85%). Germinal center B-Cell (GCB) accounted for 48.2% while Activated B-Cell (ABC) was 24.4%. Gene rearrangement was present in 26% of the patients with available data. Of the 119 (63.9%) patients who received second line treatment, only 19 (6.4%) were able to receive high dose chemotherapy and underwent an ASCT and only 3 (1%) of patients received CAR T-cell therapy. One year and two year overall survival was 47.8% and 24.7% respectively. Median OS for this population was 11.0 months. There were 105 (4.6%) relapsed patients in our cohort. Median age was 64.7 years and 96.2% were male. ECOG was 0-2 (85.7%). Stage at diagnosis was III-IV at 84.8%. Most patients had an IPI score ≥3 (80%). GCB accounted for 37.1% while ABC was 35.2%. Gene rearrangement was present for 20% of the patients with available data. In this group, 16 (15.2%) of patients received high dose chemotherapy and ASCT and only 3 (2.9%) received CAR T-cell therapy. One year and two year overall survival was 72% and 41% respectively. Median OS for this population was 21.3 months. 1403 (61%) of patients had complete response (CR) with a 1 and 2 year survival rate of 97 % and 93 % respectively and median OS of 69.3 months. Conclusion: This is one of largest data sets studying the rate of primary refractory and relapsed LBCL in the VHA and shows that more than two-thirds of these patients have high risk disease. Furthermore, a significant portion of these veterans did not receive second-line therapy including ASCT as compared to previously reported real world and clinical trial data. It is possible that our patient populations had higher rates of chemoresistance, were deemed ineligible for transplant due to age or performance status, or had higher comorbidities. Emerging data on newer antibodies and CAR T-cell therapy for early chemotherapy failure or second-line therapy might be a more appropriate option for our veteran population. In conclusion, CAR T-Cell therapy will likely replace the treatment paradigm for primary refractory or relapsed disease for early treatment failures in patients with LBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

BACKGROUND: Cutaneous T-cell lymphoma, not otherwise specified (CTCL-NOS), is a rare malignancy with limited understanding, as it is a heterogenous disease with a variable clinical course.(Hematol OncolPMID 34105822) The prognosis of this disease has been described to be independent of age at diagnosis or clinical presentation. (J Eur Acad Dermatol VenereolPMID 32997839) Due to its low incidence; there is a need for information regarding its behavior in Hispanics (HI) and Non-Hispanics (NH) in the United States (US).(Blood PMID 30635287, LeukemiaPMID 35732829) This first nationwide study aims to provide information on how demographic, clinical, and survival outcomes differ in HI versus NH patients with CTCL-NOS. METHODS: Data were analyzed on CTCL-NOS patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) 18 database between 2000-2018. SEER 18 contains the most comprehensive population-based cancer information in the US, covering approximately 27% of the total US population, and up to 36% of HI alone. Racial groups analyzed included NH whites, HI whites, blacks, and Asians or Pacific Islanders. Patient characteristics, age-adjusted incidence rate, and survival rate were compared across ethnic groups, HI vs NH. Stratification by age, gender, and stage at diagnosis was considered. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH. Multivariate analysis and propensity score matching were performed with adjustment for age, stage and B-symptoms. RESULTS: From 2000-2018, 3783 CTCL-NOS patients were diagnosed, 317 HI and 3466 NH (Table 1). Male gender predominated for both ethnicities, 52% for HI and 58% NH. HI were diagnosed at a younger median age of 54 years, in contrast to NH who were 63 years [p<0.001]. The majority of HI (34%) were diagnosed in the age bracket of 40-60 years, while the majority of NH (43%) belonged to the age bracket of 60-80 years [p=<0.001]. Patients in both cohorts were principally diagnosed from 2010-2014. Most of HI and NH were whites, but more racial diversity was noted among NH [p=<0.001]. Stage I at diagnosis predominated for HI and NH [p=0.127]. Most of the patients in both cohorts didn't receive radiation. On survival analysis; the survival probability at 2, 5 and 10 years for HI was 0.845, 0.752, and 0.637; vs for NH was 0.825, 0.706, and 0.589, respectively (Table 1). The median survival time was 14.8 years for HI, vs 15.2 years for NH. There was not a statistically difference in OS [p=0.26] (Figure 1). On multivariate analysis, when adjusted for age, patients who were older than 80 years and between 60-80 years, had worse OS compared to those younger than 60 years, with hazard ratio (HR) 8.2 [95% CI: 6 - 11] and 3.3 [95% CI: 2.6 - 4.2], respectively. Regarding stage, patients at stage III and IV, had inferior OS than those at early stages, I and II, with HR 3.3 [95% CI: 2.3 - 4.9] and HR 3.1 [95% CI: 2.4 - 4.2], respectively. CONCLUSION In this population-based analysis, no difference in OS was noted among ethnicities with CTCL-NOS. On multivariate analysis, patients diagnosed at an earlier age and stage had better OS. Notably, although HI presented at a younger age, OS was not significantly affected, which suggests that other intrinsic disease characteristics or biological factors may be driving this outcome. Better understanding of transcriptional factors, and tumor markers can help in characterizing this malignancy to create targeted algorithms for treatment. Despite the limited information available; in this SEER analysis, older age and advanced stage had an unfavorable prognosis in both HI and NH diagnosed with CTCL-NOS . Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Introduction: Diffuse large B-cell lymphoma(DLBCL) is the most common non-Hodgkin's lymphoma and its incidence steadily increases with age. The elderly population diagnosed with DLBCL are a heterogenous group with no standardized age cut-off in literature. There is also a paucity of data regarding the treatment of elderly DLBCL patients due to lack of participation and/or inclusion in clinical trials. The VHA (Veterans Health Administration) is one of the largest integrated provider of cancer care in the United States and its population, on average, is older than the general US population, giving us a unique advantage in exploring real-world outcomes in this elderly population. Methods: This is a retrospective chart review of 5199 randomly selected patients with an ICD code for lymphoma treated within the VHA between 1/1/2011 and 12/31/2019. Data abstractors collected baseline patient and disease characteristics and treatment responses. Survival time was determined via electronic health record query on 7/25/2022. Chi-square tests were used to analyze the relationship between age and variables of interest. Results: Of the 2697 patients that met the inclusion criteria, one-third of the patients were <65 years (n=916, 34%) and two-thirds of the patients were ≥65 years(n=1781, 66%) out of which 51.5%(n=1390) were within 65-79 years and 14.5% were above 80 years (n=391). Though ECOG status decreased with increasing age, more than 2/3rd of the patients within each of the above subgroups had a preserved ECOG score of 0-2. ABC phenotype was statistically more common in patients >80 years when compared to <65 years and 65-79 years as shown in Table 1. No difference was seen in the distribution of double or triple hit status between the three groups. The percentage of patients that did not receive any treatment increased with age (3.2% vs 6% vs 20.7% in <65, 65-79 and >80 year groups respectively, p<0.001), and the number of patients receiving 2 or more lines of treatment decreased with age (10.2% vs 7.5% vs 2.3%, p<0.001). Across all age groups, R-CHOP remained the common first-line regimen (73.3%, 67.9%, 39.1%) with more proportion of the >80 years group receiving R-mini-CHOP (0.3% vs 2.1% vs 15.1%) when compared to the other groups. In terms of completion of first-line treatment(R-CHOP or R-mini-CHOP), patients <65 years were more likely to complete 6 cycles when compared to patients >65-79 and 80 years (73.9% vs 67.8% vs 59.8%, p<0.001). The overall median OS decreased with increasing age, 63.7 months in <65 years, 48.3 months in 65-79 and 23.6 months in >80 years age group. Patients of all age groups, who received 6 or more cycles of first-line anthracycline-based regimen had almost double the duration of 1-, 2- year and overall survival when compared to patients who received ≤5 cycles as shown in Table 2. Conclusion: Veterans older than 65 years who are diagnosed with DLBCL present with a higher stage of disease, higher IPI score and ABC phenotype. Amongst them, the very elderly patients older than 80 years old had the shortest survival along with low treatment initiation and completion rates despite comparable functional status at diagnosis. When able to complete 6 or more cycles of first line R-CHOP/R-mini-CHOP they attained almost double the duration of median OS when compared to receiving <6 cycles of chemo-immunotherapy. Given that the incidence of DLBCL has been increasing over the age of 65 years, therapeutic approaches that optimize treatment efficacy while minimizing toxicity are needed. With the advent of genomic profiling and identification of molecular abnormalities in DLBCL, novel antibodies or small molecules with relatively low toxicity can increase tolerance in upfront setting leading more elderly patients towards completion of necessary lines of treatment and improved overall survival. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

6526 Background: Racial and ethnic disparities in access to care and outcomes are well-established and are critical issues across several malignancies, including DLBCL. Previous studies from national registry datasets have shown racial disparities in DLBCL disease characteristics, treatment and outcomes. The VHA is an equal access system providing a unique environment to investigate cancer disparities across the disease continuum. Methods: This is a retrospective chart review of 4033 randomly selected patients with an ICD code for lymphoma treated within the VHA between 01/01/2011 and 12/31/2017. Data abstractors collected baseline patient and disease characteristics and treatment responses for those with an initial diagnosis of DLBCL in that time frame. Survival time was determined via electronic health record query on 11/30/2021. Chi-square tests were used to analyze relationship between race and variables of interest. Cox proportional hazards model was used to estimate hazard ratios (HR) for race and controlling factors. Results: 2141 DLBCL patients met our inclusion criteria. 97% were male. Majority were Non-Hispanic Whites (NHW 75%) followed by Non-Hispanic Blacks (NHB 12.5%), Hispanics (H 5.7%) and others (O 6.8%). NHB were diagnosed at younger median age (63 years) when compared to the NHW, H and O (68 years). There was no statistically significant difference in stage at diagnosis, IPI score, cell of origin (COO) and hit status amongst racial subgroups. Outcomes analysis (Table) revealed similar treatment and response rates, median OS, 1- and 2- year survival across all racial subgroups. However, after adjusting for age, IPI, COO, and exposure to agent orange, and including up to 10-years of survival data, H had 36% lower risk of death (HR=0.64, 95% CI 0.44-0.93) than NHW, while NHB and O had similar outcomes to NHW. Conclusions: This large retrospective study is a continuation of our group’s work (Williams et al, 2020) that doubles the cohort size and confirms that when standard of care therapy is given with equal access to care, short-term treatment and survival outcomes are same for all races. Further studies are needed to analyze risk factors associated with differences in long term outcomes.[Table: see text]