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TPS294 Background: Approval of [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy, was based on the results of the Phase 3 VISION study (NCT03511664). It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related risks. To this end, the long-term follow-up (LTFU) safety study (NCT05803941) has been established. Findings from the LTFU study will be crucial for assessing delayed toxicities for patients with PSMA-positive metastatic prostate cancer treated with 177 Lu-PSMA-617 globally. Methods: The LTFU study is a prospective, multi-center, non-EU post-authorization safety study. Patients who received ≥1 dose of 177 Lu-PSMA-617 within one of the prospective parent studies (Table 1) are eligible. Patients may enroll in the LTFU study after fulfilling the requirements of their corresponding parent study. The primary endpoint is the number and proportion of selected adverse events (AEs), including myelosuppression, xerostomia, renal failure, xerophthalmia, and second primary malignancies (eg, myelodysplastic syndrome or acute myeloid leukemia), other serious AEs, and changes in laboratory values. The secondary endpoint is the number and proportion of deaths. Following enrollment, patients will undergo assessments at baseline, and then every 6–8 months for up to 10 years after their first dose of 177 Lu-PSMA-617 or until death. At each visit, a review of selected treatment-related AEs (xerostomia, xerophthalmia, myelosuppression), any-cause AEs (renal toxicity, new diagnoses of second primary malignancies), and treatment-related serious AEs will be conducted. Physical and laboratory assessments, as well as details on concomitant medications and interventions, including anti-cancer therapies, will be collected. Patients may receive treatment with any medical intervention. Interim analyses are planned at 2 and 5 years post-study activation. Enrollment is ongoing (n=13). Clinical trial information: NCT05803941 . Parent studies of the long-term follow-up safety study. Trial Indication Phase N (all groups) ClinicalTrials.gov ID VISION (+sub-study) Post-taxane mCRPC 3 831 (+30) NCT03511664 PSMAfore Pre-taxane mCRPC 3 469 NCT04689828 PSMAddition mHSPC 3 1144 NCT04720157 177 Lu-PSMA-617 in patients with moderately or severely impaired, or normal renal function Post-taxane mCRPC 2 20 a NCT06004661 a Planned. mCRPC, metastatic castration-resistant prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer.

727 Background: Despite the availability of targeted therapies like erdafitinib for pts with aUC with susceptible genomic alterations, the rate of NGS testing remains low at 32% in the United States (Hage Chehade...Swami, JAMA Network Open, 2024). Furthermore, limited data exist regarding the timing of NGS testing in relation to the time of death. Herein, we sought to assess the rates of NGS testing at the end of life in pts with aUC in a real-world patient population. Methods: A de-identified nationwide Flatiron Health electronic health record (EHR)-derived database was used to extract patient-level data. Inclusion criteria: pts who received NGS testing (blood/tissue) and who had a date of death recorded. The analytic cohort included pts diagnosed with aUC between 1/1/2011 and 11/14/2022 who received first NGS testing results between 5/3/2012 and 12/21/2022. The time difference between each pt’s first NGS result delivered and death was calculated, and thereafter, pts were categorized into 3 categories: pts receiving results > 3 months (mo) before death, within 3 mo of death, or after death. The frequency and percentages of the 3 categories were reported, as well as by year of death. The percentages in each category were compared between 2019 (year of erdafitinib approval) and 2022 (last year in dataset) to evaluate changes in NGS testing trend. Results: Among 12,157 pts with aUC in the dataset, 1,637 had both a recorded date of death and underwent NGS testing, and were eligible and included in final analysis. The median age was 72 (IQR 66 – 79). The majority were male (73%), White non-Hispanic (76%), and treated in community practice (86%). 68.2% received NGS results > 3 mo before death (n = 1,117), 28.3% received results within 3 mo of death (n = 464), and 3.4% of NGS results were reported after death (n = 56). In pts who died in 2019 versus 2022, the percentage of pts receiving NGS results > 3 mo before death increased from 61% to 75%, while the percentage of pts receiving results within 3 months decreased from 33% to 22%, and the percentage of NGS results reported after death declined from 5.2 to 2.7%. Baseline characteristics (including race-ethnicity, insurance plan, practice type [academic vs. community]) in these categories will be presented at the meeting. Conclusions: Our findings suggest that a sizeable number of pts with aUC (∼ 32%) received their first NGS testing results towards the end of life, highlighting the need to integrate genomic testing earlier during the course of the disease to optimize benefit with targeted therapies. These results could inform clinical practice and therapeutic decisions in the clinic. CHC, YJ: Equal contribution; US, NA: Senior authors.

108 Background: PARPi are approved for the treatment of pts with mCRPC either as single agents or as a combination with an androgen receptor pathway inhibitor (ARPI) [PMID: 37442702]. In a US Food and Drug Administration (FDA) pooled analysis, the benefit from PARPi appeared greatest for pts harboring BRCA1/2 alterations [PMID: 38484203]. However, real-world uptake of PARPi in pts with mCRPC with BRCA1/2 alterations is unknown. Herein, our objective was to assess the usage of PARPi in real-world pts with mCRPC harboring BRCA1/2 alterations. Methods: A de-identified nationwide Flatiron Health electronic health record (EHR)-derived database was used to extract pt-level data. Eligibility criteria: pts with mCRPC harboring alterations in BRCA1 or BRCA2 or both and alive after 8/15/2020 (i.e., 3 months following the approval of the first PARPi, rucaparib, in mCRPC) with available treatment information. The data cutoff date was 5/31/2024. Pts were categorized into two cohorts based on the receipt of any PARPi or not. Baseline characteristics at the time of mCRPC diagnosis, including age, race-ethnicity, and insurance plan, were collected in both cohorts. Results: Of the overall cohort of 24,105 pts with metastatic prostate cancer, 443 pts had mCRPC with BRCA1/2 alterations and were eligible and included in this analysis. 227 (51.2%) received a PARPi, while 216 did not (48.8%). Among the 227 pts who received a PARPi, 166 received it as a single agent (73.1%), 40 received it in combination with an ARPI (17.6%), and 21 received it in combination with other agents (9.3%). The median age was 72 in both cohorts (IQR 65 – 79 in patients receiving a PARPi and 66 – 78 in patients who did not). Other baseline characteristics in both groups are shown (Table). Conclusions: Despite PARPi demonstrating survival improvement in pts with mCRPC with BRCA1/2 alterations, a significant proportion of pts do not receive them. Our findings highlight the need to improve education among clinicians of level 1 evidence and improve access to life-prolonging therapies in pts with mCRPC. Baseline characteristics of pts with mCRPC who received vs. did not receive a PARPi. Characteristic Subgroup Pts who received a PARPiN = 227 Pts who did not receive a PARPiN = 216 Race-ethnicity, n (%) Asian 9 (4) 1 (0.5) Black 22 (9.7) 30 (13.9) Hispanic-Latino 10 (4.4) 10 (4.6) White 149 (65.6) 124 (57.4) Other and unknown 37 (16.3) 51 (23.6) Insurance, n (%) Commercial health plan 192 (84.5) 182 (84.3) Medicare-other government programs 31 (13.7) 18 (8.3) Medicaid 1 (0.4) 3 (1.4) Others and unknown 3 (1.3) 13 (6)

104 Background: Androgen deprivation therapy (ADT) intensification [ADT + androgen receptor-pathway inhibitor (ARPIs) +/- docetaxel] has been shown to improve survival outcomes in pts with mHSPC and is recommended as standard of care by all major guidelines. However, prior studies have shown underutilization of ADT intensification [PMID: 39191549]. There are limited updated and large-scale studies on the use of ADT intensification, beyond January 2023. In this study, we aimed to assess the treatment patterns of ADT intensification in real-world pts with mHSPC in the US, including data on those treated since January 2023. Methods: This retrospective study utilized the nationwide Flatiron Health Electronic Health Record (EHR) derived de-identified database. Eligibility: Pts diagnosed with mHSPC and availability of treatment information (ADT and/or line of therapy in mHSPC). The data cut-off date was 5/31/2024. Treatment patterns were summarized using frequency and percentages. All analysis was done using R version 4.2.3. Results: Among 24,105 pts with metastatic prostate cancer in the database, a total of 14,084 were eligible and included. The median age at metastatic diagnosis was 72 years (IQR 65 – 79), and 60% were White non-Hispanic. In the overall cohort (1/1/2013–5/15/2024), 56.8% received ADT monotherapy, and 37.7% received ADT intensification. Table summarizes the treatment patterns by year, highlightinga consistent increase in adoption of intensified ADT regimens, and a decline in use of ADT monotherapy. Notably, since January 2023, 76.8% pts with mHSPC received ADT intensification while only 17.3% of pts received ADT monotherapy. Conclusions: To our knowledge, this is the first and largest study to evaluate the current use of ADT intensification. These data indicate a notable improvement in the adoption of level 1 evidence (ADT intensification) in the treatment of pts with mHSPC. These encouraging data emphasize the benefits of continued efforts to promote guideline-concordant care and provide the current treatment landscape to design clinical trials. Treatment patterns by year in pts with mHSPC. Treatment 2013–2017n = 5,263(%) 2018n = 1,313 (%) 2019n = 1,407(%) 2020n = 1,353(%) 2021n = 1,483(%) 2022n = 1,556(%) 2023n = 1,459(%) 2024n = 250(%) ADT monotherapy 4,095 (77.8) 856 (65.2) 819 (58.2) 664 (49) 698 (47.1) 569 (36.6) 291 (20) 5 (2) ADT + ARPI 155 (2.9) 238 (18) 354 (25.1) 452 (33) 555 (37.4) 695 (44.7) 842 (58) 154 (61.6) ADT + Docetaxel 709 (13.5) 156 (12) 175 (12.4) 156 (12) 134 (9.0) 117 (7.5) 78 (5.3) 19 (7.6) Triplet(ADT + ARPI + Docetaxel) 6 (0.1) 2 (0.2) 1 (0.1) 2 (0.1) 9 (0.6) 82 (5.2) 166 (11.1) 53 (21.2) Other therapies 298 (5.7) 61 (4.6) 58 (4.1) 79 (5.8) 87 (5.9) 93 (6) 82 (5.6) 19 (7.6)

ABSTRACTObjectivesThis final post hoc analysis evaluated patient‐reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D‐Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5‐month follow‐up in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.MethodsKey scales from the EORTC QLQ‐C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.ResultsThe intent‐to‐treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D‐Rd‐treated patients showed improvements from baseline that were sustained over 5 years in the intent‐to‐treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D‐Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16–2.91]), physical functioning (1.93 [1.18–3.14]), pain (1.41 [0.90–2.22]), and fatigue (2.00 [1.24–3.23]). Greater proportions of patients with bone lesions improved with D‐Rd versus Rd on GHS and physical functioning.ConclusionsIn transplant‐ineligible patients with NDMM, D‐Rd improved health‐related quality of life over a 5‐year period versus Rd. Trial Registration: ClinicalTrials.gov: NCT02252172

This cohort study conducted among Minnesota children diagnosed with adrenoleukodystrophy through newborn screening examines correlation of C26:0 lysophosphatidylcholine (C26LPC) with clinical phenotype over 5 years and recommends adjusting early childhood surveillance regimens in children with lower C26LPC levels.

Abstract Background Cholangitis is a well-described adverse event (AE) following endoscopic retrograde cholangiopancreatography (ERCP) that is associated with significant morbidity and mortality. Despite this, contemporary characterization of this AE using high-quality prospective data is incomplete. Aims In this study we describe post-ERCP cholangitis incidence, risk factors, and outcomes in a large, international multicenter population of patients undergoing ERCP. Methods We analyzed prospective data from nine centers in Canada, USA, and Europe between 2018-2024 with 30-day follow-up. The primary outcome was post-ERCP cholangitis, defined as (1) temperature &lt;36.0°C or &gt;38.0°C or white blood cells &lt;4 x109/L or &gt;10x109/L, (2) accompanying rise in bilirubin or transaminases to &gt;1.5 times the upper limit of normal or any increase compared to pre-procedure, and (3) emergency department visit or hospital admission and/or prolongation of existing admission. Multivariable logistic regression was performed to identify risk factors, with results presented as odds ratios (OR) with associated 95% confidence intervals. Outcomes following cholangitis were also described. Results Post-ERCP cholangitis occurred following 134 (1.7%) of 8,119 ERCPs (mean onset of symptoms 2.0 days). Repeat ERCP was required in 53.7% of these cases. Mortality attributed to cholangitis occurred in 8.2% of incident cases. Male sex (OR 1.48, 1.02-2.19), longer procedural time (OR 1.01, 1.00-1.02 per additional minute) and presence of a biliary stricture (OR 3.24, 1.98-5.30) were all independent risk factors for post-ERCP cholangitis, while placement of a biliary stent (OR 0.59, 0.36-0.95), and biliary sphincterotomy (OR 0.59 0.39-0.87) were both protective against post-ERCP cholangitis. Conclusions Post-ERCP cholangitis is common and associated with high mortality rates. Adequate pre-procedural counseling and early recognition is advised, especially in patients at increased risk. Funding Agencies None

Background Carotid artery tortuosity (CAT) may complicate mechanical thrombectomy (MT), potentially causing delays or preventing recanalization. However, the relationship between CAT and MT outcomes remains largely unexplored. This systematic review aims to evaluate the existing evidence regarding the impact of CAT on MT outcomes. Methods Following PRISMA guidelines, a systematic literature search was conducted using MEDLINE, EMBASE, Web of Science, Cochrane, and Scopus databases. Studies providing data for MT outcomes based on CAT status were included. Outcomes of interest included successful recanalization, first-pass efficacy (FPE), procedure time, functional independence, and procedure-related complications. Results Our search identified nine studies with 2737 patients. Three studies employed DSA to assess tortuosity, whereas the remaining six studies preferred CTA. In seven studies, CAT was associated with prolonged procedure times. In five studies, successful recanalization rates were significantly lower in CAT patients as compared to patients with non-tortuous arteries. Two studies showed that CAT could alter FPE or successful recanalization rates of first-line MT techniques. No study found statistically significant relationships between CAT and functional independence. Three studies examined the association between CAT and safety outcomes, and only one study found increased intracranial hemorrhage rates in patients with CAT. All nine studies employed different CAT criteria. Conclusions Despite the vast MT literature, the number of studies reporting CAT status remains low. CAT may affect procedure time and technical outcomes of MT. Therefore, employing a uniform CAT definition and reporting CAT more frequently can provide insights into management of patients with acute large vessel occlusions.