In PDAC, VsT can frequently present as an incidental finding on routine abdominal imaging. The most common location is PV, followed by MV and SV. We observed that AC is underutilized in this setting despite a low bleeding complication rate. PV was associated with the least overall survival of the VsT. Future large prospective studies should explore the role of AC and value in this setting.

Background Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin lymphoma that is often associated with immunosuppressed states. The Epstein-Barr Virus (EBV) may play a role in tumor pathogenicity in some cases. The objective of this study was to examine the patient characteristics, tumor pathology, and survival outcomes associated with EBV tumor status in patients with PCNSL. Methods This was a retrospective subset analysis from 17 academic medical centers that included 439 patients of ages 60 years and above with PCNSL (David K et al. ASH 2020). The associations between EBV status and clinical or demographical variables were tested by Fisher's exact test, Wilcoxon rank-sum test, or CMH trend test. Kaplan-Meier estimator was used to estimate survival probability. Survival difference between groups was tested by log-rank test for statistical significance. Confidence interval of survival rate was calculated using Greenwood's formula. Results A total of 247 patients with available EBV status were included in this analysis. Median age was 71 (range 60-84) and 44.5% were male. Notably, none of the patients were HIV-positive. Twenty-five patients (10.1%) had EBV positive tumors as detected by EBER (EBV-encoded RNA) in-situ hybridization or LMP1 immunohistochemistry (IHC), 17 of which were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD) and 8 of which were not PTLD. All EBV-positive non-PTLDs were diffuse large B-cell lymphoma. Three (15%) SOT-related PTLDs were EBV-negative. Patient characteristics analyzed included age at diagnosis, sex, ECOG performance status, history of prior or concurrent malignancies, history of solid organ transplant or autoimmune disease, history of allogeneic stem cell transplant, and immunosuppressive treatment. Of these, only a history of solid organ transplant or autoimmune disease (P<0.0001) and immunosuppressive treatment (P<0.0001) were highly correlated with EBV-positivity; there were no other patient factors associated with EBV status. For patients with EBV-positive SOT-related PTLD, the most common immunosuppressive medications were mycophenolate (n=13), calcineurin inhibitors (n=11), and prednisone (n=9). Only 1 of the EBV-positive non-PTLD cases had a history of autoimmune disease and was on mycophenolate and hydroxychloroquine. Tumor characteristics analyzed included expression of C-MYC, BCL2, CD5, cell of origin markers (BCL6, MUM1, CD10), and CD20 through IHC, C-MYC and BCL2 translocation through FISH, histology, and involvement of brain parenchyma, CSF, spinal cord, and eyes. EBV-positive tumors were associated with low C-MYC (p=0.047) and BCL6 (p=0.0006) expression on immunohistochemistry, but not other factors. There were no significant differences in tumor characteristics between those with EBV-positive PTLD and EBV-positive non-PTLD. Among patients with PTLD, 30% (n=6) did not receive primary chemotherapy, and the most common treatment regimens were high-dose methotrexate (HD-MTX) with or without rituximab (n=5) and rituximab alone (n=3). However, there was no significant difference in outcomes among PTLD patients who received chemotherapy or those who did not. Among EBV-positive non-PTLD patients, only 12.5% (n=1) did not receive primary chemotherapy and the most common treatment regimens were methotrexate/rituximab/temozolomide (n=3) and HD-MTX with or without rituximab (n=3). There was no difference in overall or progression free survival between patients with EBV-positive and EBV-negative tumors, or in outcomes among SOT-related PTLD patients regardless of EBV status. However, patients with EBV-positive non-PTLD PCNSL had better overall survival compared to patients with EBV-positive PTLD and EBV-negative tumors (p=0.033, Figure). Conclusions In this large observational study of older patients with PCNSL, the incidence of EBV positive tumors was overall low and was most commonly associated with SOT-related PTLD. Mycophenolate mofetil was the most common immunosuppressive medication. In those without PTLD, there were no patient or tumor factors that were associated with EBV status. Unexpectedly, non-PTLD EBV-positive PCNSL had superior outcomes to EBV-positive PTLD and EBV-negative PCNSL. Future studies of EBV-positive non-PTLDs are warranted to further evaluate the potential impact of EBV latency and the immune response on the tumor microenvironment. Disclosures Reddy: BMS: Consultancy, Research Funding; Celgene: Consultancy; Abbvie: Consultancy; Genentech: Research Funding; KITE Pharma: Consultancy. Bachanova:Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; FATE: Research Funding; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bond:Seattle Genetics: Honoraria. Goldlust:Tocagen: Membership on an entity's Board of Directors or advisory committees, Other: travel; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel; WEX: Consultancy, Other: travel; Cortice Bio: Consultancy, Other: travel; Boston Biomedical: Consultancy; COTA: Other; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel, Research Funding, Speakers Bureau. Spurgeon:Gilead: Research Funding; Genentech: Research Funding; Cardinal Health: Honoraria; Bristol-Myers Squibb: Research Funding; VelosBio: Consultancy, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Research Funding; AstraZeneca: Research Funding; Pharmacyclics: Consultancy; Beigene: Research Funding; Verastem: Research Funding; Genmab: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Karmali:AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding; BeiGene: Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Smith:Janssen: Consultancy; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; BMS: Consultancy; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding. Rubenstein:Kymera: Research Funding. Kahl:BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy. Evens:Abbvie: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria, Research Funding; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding. Martin:Kite: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; Bayer: Consultancy; I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; Celgene: Consultancy.

No abstract

6519 Background: HRQoL data in cancer clinical trials can inform tolerability of new drugs, facilitate informed decision-making, and influence health care and policy decisions, but are frequently underreported. We reviewed all registration trials that informed Food and Drug Administration (FDA) approval between 2015-2020 for latency and quality of HRQoL reporting. Methods: HRQoL data for each clinical trial associated with FDA drug approval between 7/2015-5/2020 was collected retrospectively from multiple sources including the FDA and clinicaltrials.gov website, conference abstracts, and journal manuscripts. The aim of the study was to analyze the proportion of trials reporting HRQoL, quality of HRQoL data, latency between FDA approval and first reporting of HRQoL data, and association between changes in HRQOL and overall survival (OS) and progression-free survival (PFS) outcomes. Results: Of the 259 trials involving 245 drug approvals, majority involved solid tumors (61.4%), were phase III (59.1%), and led to approval based on a non-PFS/OS endpoint (52.9%). HRQoL was a pre-specified endpoint in 55.2% and reported in 49.8% trials. HRQoL data was published by the time of FDA approval in only 41.8% cases, 24.8% reported HRQoL data > 12 mo after approval. Further, among trials reporting HRQoL (n = 129), HRQoL data was first reported in the primary paper in only 34.1%, and either in an ancillary paper in 41.9% or an ancillary abstract in 24% trials. Of the 129 trials with HRQoL data, an improvement in HRQoL was seen in 44.2%, no significant change in 41.9%, mixed results in 11.6%, and worsening in 2.3% of trials. Overall, by the time of FDA approval, OS and PFS data were reported in 59% (152/259) and 65% (168/259) trials respectively with an OS benefit seen in 23.9% (62/259) trials, and PFS benefit in 38.6% (100/259) trials. Of the 84 trials that led to FDA approvals based solely on response rate, HRQoL was reported in only 23.8% (n = 24) with a HRQoL benefit seen in only 9.5% (n = 8) trials. Trials reporting either no significant impact on HRQoL or a mixed impact on HRQoL reported median OS benefit of 4.6 months and 4.2 months respectively. In trials reporting HRQoL data > 6 mo from FDA approval, OS benefit of < 3 mo was seen in 17.8% (8/45) trials. No significant time trends were noted during the study period. Conclusions: There was significant underreporting of HRQoL outcomes in trials ( < 50%) associated with FDA drug approvals between 2015-2020 with majority of trials reporting HRQoL data in an ancillary paper/abstract, and at a much later time than the FDA approval. While it is widely accepted that timely dissemination of HRQoL data from cancer drug trials are vital for clinical and regulatory decisions, no improvement in reporting rates were noted over past 5 years. Only 10% of drugs approved on the basis of response rates showed improvement in HRQoL in the registration trials.

Introduction: Treatment of older patients (pts) with PCNSL is challenging due to the prevalence of comorbidities, frailty, and complexities with delivery of chemotherapy (CT). The optimal induction CT and consolidation regimens for older PCNSL pts is unknown. Moreover, there are few large scale prognostication studies available, including analysis of geriatric assessments (GA). We analyzed detailed characteristics, treatment patterns and outcomes with prognostication across 17 academic centers. Methods: We conducted a large, RW retrospective study of newly diagnosed PCNSL pts (1/2008-1/2019) ages ≥ 60 years (yrs). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. We detailed Cumulative Index Rating Scale-Geriatric (CIRS-G) scores & other GAs. Univariate associations were derived via Cox model with variables p&lt;0.05 entered stepwise into a multivariate (MVA) model. Results: Among 491 initial cases, n=450 cases were verified for diagnosis & follow-up. Clinical features included: median age 71 yrs (60-88); male 47%; elevated LDH 30%; creatinine clearance &lt;60 ml/min in 20% (median 81 ml/min); hemoglobin &lt;10 g/dL in 8%; and albumin &lt;3.5 g/dL in 35%. 21% of pts had prior or concurrent malignancy and 7% had history of solid organ transplant or autoimmune disease. Histology was DLBCL in 96% (COO non-GC in 76%) with CD20 expression seen in 98%. Immunohistochemistry showed MYC & BCL2 double expression in 40%; EBER was noted in 10% of pts (3/4 being PTLD pts). For disease location, brain parenchyma was involved in 94% of pts with 46% having a single site (54% &gt;1 site). Cerebral involvement predominated in 75% with deep structure involvement in 20% & cerebellum in 5%. CSF involvement was documented in 13% of pts (unchecked in 26%). For GA at diagnosis, the median CIRS-G score was 6 (range 0-27) and impaired self-care activities of daily living (ADLs) were noted in 36%. Furthermore, geriatric syndrome (ie, dementia, delirium, depression, and/or falls) was present in 45% of pts. Induction therapy included CT in 91% of pts (of whom 82% had rituximab (Rtx)) and radiation therapy (RT) in 8%. The most common chemotherapy regimens were: high-dose methotrexate (HD MTX) or HD MTX with Rtx (MR) in 38%; HD MTX/procarbazine/vincristine (MPV) +/- Rtx 30%; HD MTX/temozolomide/Rtx (MTR) 22%; Rtx alone 2%; and HD MTX/cytarabine/thiotepa/Rtx (MATRIX) in 2%. Median MTX dosing for all pts was 3.5 g/m2 (range 1-8 g/m2), and by 3 most common regimens (all g/m2): MTR 5.1; MR 5.4; MPV 3.1 (P&lt;.0001). For response to induction, 60% had complete response (CR), 18% partial response (PR), 6% stable disease & 16% had primary refractory disease. Induction CT was stopped due to toxicity in 21% of pts and the treatment-related mortality was 7%. Among 321 pts with CR or PR, 14% had autologous stem cell transplant (ASCT); 25% received consolidative CT; and 5% had RT. The most common CT maintenance regimens were temozolomide (n=22), lenalidomide (n=20) and HD MTX (n=15). Among pts experiencing relapse or progression, the most common 2nd line therapies were RT (n=40), MTX (n=39), temozolomide (n=14) and MTR (n=10); 2 pts ultimately went on to receive ASCT. With 42 month median follow-up (1-125), 3-yr PFS & OS for all pts were 38% & 52%, respectively (Fig 1A/1B). On MVA, factors associated with inferior PFS were: advancing age (continuous HR 1.05, P&lt;.001); anemia (HR 1.14, P=.0035); high CIRS-G (HR 1.038, P=0.017) and geriatric syndrome (HR 1.537, P=.0098) (Fig 1C); and for inferior OS: advancing age (continuous HR 1.04, P=.01); low albumin (HR 2.203, P&lt;.001); high CIRS-G (HR 1.053, P=.011); and geriatric syndrome (HR 1.851, P=.005) (Fig 1D). Among all pts, increasing HD MTX dosing in 500 mg/m2 increments was associated with improved PFS (HR 0.958, P=.0002) & OS (HR 0.954, P=.001); and pts treated with MTR had improved PFS & OS vs MPV or MR (Fig 1E /1F). The favorable effect of MTR vs MR persisted when controlling for age, CIRS-G & geriatric syndrome. Additionally, use of Rtx was associated with improved outcomes (PFS HR 0.592, P&lt;.0001; OS HR 0.528, P&lt;0.0001). Finally, pts achieving CR had significantly improved survival (Fig 1G/1H). Conclusions: Older pts with PCNSL have suboptimal outcomes, with 2/3 progressing in the first several years. GA is an important prognostic tool, and could be used to stratify pts in future investigations. In addition, use of Rtx, increasing MTX dose, and the MTR regimen were associated with improved outcomes. Disclosures Reddy: Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy; Celgene: Consultancy; BMS: Consultancy, Research Funding. Bachanova:Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; FATE: Research Funding; BMS: Research Funding; Incyte: Research Funding. Bond:Seattle Genetics: Honoraria. Goldlust:COTA: Other; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel; Tocagen: Membership on an entity's Board of Directors or advisory committees, Other: travel; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel, Research Funding, Speakers Bureau; Boston Biomedical: Consultancy; Cortice Bio: Consultancy, Other: travel; WEX: Consultancy, Other: travel. Spurgeon:Beigene: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Acerta: Research Funding; AstraZeneca: Research Funding; Genmab: Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Karmali:Takeda: Research Funding; Karyopharm: Honoraria; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Martin:Celgene: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Teneobio: Consultancy; Beigene: Consultancy; Cellectar: Consultancy; Incyte: Consultancy; Kite: Consultancy; Morphosys: Consultancy; Karyopharm: Consultancy, Research Funding; Regeneron: Consultancy. Smith:Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; FortySeven: Research Funding; Karyopharm: Consultancy, Research Funding; Pharmacyclics: Research Funding; BMS: Consultancy; Janssen: Consultancy; Celgene: Consultancy, Research Funding; Acerta: Research Funding. Rubenstein:Kymera: Research Funding. Kahl:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Pharmacyclics LLC: Consultancy; Roche Laboratories Inc: Consultancy; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding. Evens:Merck: Consultancy, Honoraria, Research Funding; Research To Practice: Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria.