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Phase 1 study of META 10-19, an IL-10-expressing, anti-CD19 CAR T cell product in patients with high-risk DLBCL.
2552 Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B cell lymphoma. However, limited duration of remission remains a significant challenge. We designed a metabolically armored anti-CD19 CAR T-cell product (META 10-19) that autocrine interleukin (IL)-10 to enhance antitumor activity, and assess the therapeutic potential in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Methods: This phase 1 study is designed to evaluate the safety and preliminary efficacy of META 10-19 in relapsed/refractory DLBCL patients aged 3–70 years old. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASTCT criteria, and other adverse events (AEs) were evaluated according to CTCAE 5.0. Tumor response was assessed by investigators using Lugano 2014 criteria and IPCG criteria. Results: From December 2022 to December 2024, 14 patients with a median age of 54.5 years have been enrolled and received META 10-19 infusion at doses ranging from (0.002–0.1) ×10 6 cells/kg, following a standard lymphodepletion regimen (30 mg/m 2 /day Flu ×3 days, 300 mg/m 2 /day Cy ×3 days). All patients had relapsed/refractory disease, with high-risk features including primary refractory (n = 9), nodal and extranodal involvement (n = 6), CNS lymphoma (n = 5), and bulky disease (n = 2). The most frequent Grade 3–4 AEs comprised neutropenia (100%, 14/14), thrombocytopenia (85.7%, 12/14), and anemia (71.4%, 10/14). CRS was predominantly manifesting as low-grade events (Grade 1–2, n = 13; Grade 3, n = 1). ICANS developed in 2 patients (14.3%) with primary CNS disease, manifesting as transient seizures and classified as Grade 3. At 3 months post-infusion, the overall response rate was 100%, including 13 patients (92.9%) achieved complete response (CR), and 1 patient achieved partial response. As of December 1, 2025, with a median follow-up of 23.3 months (range, 5.6–33.4), 9 patients maintained CR for over 1 year, 4 for over 2 years, and the earliest infused patient remains in remission at 33.4 months. The median progression-free survival (PFS) and overall survival (OS) have not yet been reached, while the 12-month PFS rate and 12-month OS rate were 71.4% and 92.9% , respectively. Conclusions: This first-in-human trial of META 10-19, an IL-10 expressing, anti-CD19 CAR T-cell product, for the treatment of relapsed/refractory DLBCL has exhibited manageable safety profile and durable efficacy at ultra-low doses in patients with high-risk features. Studies evaluating larger cohorts and longer follow-up are ongoing. Clinical trial information: NCT05715606 .
A phase II trial of olaparib in combination with pembrolizumab in metastatic uveal melanoma.
9553 Background: Metastatic uveal melanoma (mUM) has a poor prognosis with modest response to immune checkpoint blockade (ICB). Inactivating mutations in BRCA-1 associated protein 1 ( BAP1 ) are common in mUM leading to deficient homologous recombinant DNA repair and increasing reliance on alternate repair pathways, including poly[ADP-ribose] polymerase (PARP). We investigated if the PARP inhibitor olaparib could improve objective response to pembrolizumab (PEM) in mUM (NCT05524935). Methods: Key eligibility included mUM with measurable disease, ECOG 0-1, and adequate organ function. Prior liver directed therapy was allowed. Patients (pts) received PEM 200mg IV every 21 days plus oral olaparib 300mg BID till progression, toxicity, or completion of 2 years of treatment. In a Simon 2-stage optimal design, > 1 response by RECIST 1.1 in 12 evaluable patients would permit accrual to expand to 37 pts. Results: Twelve eligible mUM pts, 6 male and 6 female, median age 59 years (42, 84) were treated in stage 1 of this trial. Most pts (11/12; 92%) had both liver and extra-hepatic metastatic disease; 5 pts had elevated serum LDH at baseline. Seven pts (58%) were naïve to prior systemic therapy; 4 had prior liver directed therapy. There was no objective response observed; best response was stable disease (SD, n=5), remainder (n=7) with progression; disease-control rate was 42%. One patient continues treatment at 13 months with ongoing SD. Of 4 pts who received prior tebentafusp, three had SD lasting greater than 6 months. At median follow-up of 13 months, the median progression-free survival (PFS) was 3.6 months (95% CI: 2.2, 8.3), and median overall survival (OS) was 13.8 months (95% CI: 2.5, 24.3). Six-month PFS and OS were 0.42 (95% CI: 0.15, 0.67) and 0.83 (95% CI: 0.48, 0.96) respectively; one year OS was 0.73 (95% CI: 0.37, 0.91). Most common (≥ 25%) all grade treatment related adverse events (AEs) were fatigue, arthralgia, diarrhea, nausea/vomiting, dyspnea, anemia, abdominal pain, bloating, anorexia, muscle weakness, pruritus, rash, vitiligo, dyspnea, cough, hypertension, muscle weakness, ↑ AST, ↑ alkaline phosphatase, ↓ lymphocyte count, ↑ glucose, ↑ potassium and ↓ albumin. Grade 3 AEs were infrequent; nausea, anorexia, dehydration, hypotension, and muscle weakness (all n=1); there was no treatment related death. 5/12 (42%) pts required a dose reduction for olaparib. Conclusions: The addition of olaparib to pembrolizumab was well tolerated but did not result in any objective response in molecularly unselected mUM. Landmark survival results appear clinically meaningful and likely related to disease control with stable metastatic burden. Ongoing biomarker studies of tumor tissue (BAP1, PD-L1, PARP1, TIL) and blood may help discern which patients could benefit from this combination regimen. Optimal sequencing of ICB with tebentafusp in HLA-A*02:01+ mUM should be explored further. Supported by Merck, Inc. Clinical trial information: NCT05524935 .
Dominant chromosomal abnormalities in breast cancer metastasis to CNS as compared with systemic metastasis demonstrated by liquid biopsy.
1035 Background: Breast cancer (BrC) central nervous system (CNS) metastases are believed to be biologically and therapeutically distinct from systemic metastases. Detecting BrC metastasis to CNS using liquid biopsy (LBx) of the CSF is emerging as a reliable approach not only for confirming metastasis, but also for defining the molecular and biological characteristics of this metastasis. We compared the findings of LBx performed on CSF with those obtained by peripheral blood (PB) LBx. Methods: LBx was performed by next generation sequencing (NGS) of cell-free DNA and RNA (cfDNA/cfRNA) in PB plasma or CSF as well as RNA sequencing of CSF cell pellet. RNA sequencing was performed using a panel of almost 1600 genes and DNA sequencing using 302 genes. Results: Of the 339 tested CSF samples, 29 (8.5%) were negative for any mutation and 57 (16.8%) showed low level mutations characteristic of CHIP (clonal hematopoiesis of indeterminate potential). However, two samples showed only chromosomal gain or loss without mutations and 2 showed chromosomal abnormalities with CHIP but no cancer-related mutations. In contrast, 19 of 279 PB samples (6.8%) were negative for any abnormality and 33 (11.8%) had CHIP. One sample of the PB cases showed chromosomal abnormalities without cancer-related somatic mutations. Of the 253 positive CSF samples 207 (82.1%) showed chromosomal structural abnormalities while only 71 of the 227 positive PB samples (31.2%) showed chromosomal structural gain or loss (P <0.0001). The most common chromosomal abnormality was 1q gain, detected in 42.8% of CSF and in 18.5% of PB samples. 17p (TP53) deletion was detected in 25.4% of CSF and in 6.6% of PB samples. 10q (PTEN) deletion was detected in 9.4% of CSF and 3.1% of PB samples. ERBB2 gene amplification was detected in 6.3% of CSF cases and in 1.3% of PB cases. In CSF positive samples, the most mutated genes were TP53, KMT2C, PIK3CA, DNMT3A, CDH1, NF1, PTEN and ESR1, detected in 37.3%, 29%, 27.8%, 10.3%, 8.7%, 8.3%, 7.9%, and 7.5%, respectively. These genes were detected in positive PB samples at 51%, 35.2%, 42.7%, 81.1%, 11.8%, 8.8%, 9.6%, and 20.2%, respectively. Variant allele frequency in all mutations was significantly higher in CSF (P=0.0001) than PB. Germline mutations in BRCA1/2 were detected in 5.1% of CSF and in 4.8% of PB. Ten patients had their PB and CSF tested concurrently. Two were positive by CSF and negative by PB and one was positive by PB but negative by CSF. The rest had concordant results. Conclusions: BrC with CNS involvement represents a distinct subgroup whose biological characteristics may best be defined using LBx to evaluate chromosomal abnormalities and gene gain/loss. As such, optimal characterization and qualification minimal residual disease in patients with BrC with CNS involvement warrants integration of CSF LBx-defined genetic abnormalities as it may permit earlier and targeted interventions.
RET fusion–positive lung adenocarcinoma: Partner-specific clinicopathological characteristics, co-mutation profiles, and implications for targeted and immunotherapy.
8615 Background: RET fusions represent actionable oncogenic drivers in lung adenocarcinoma (LUAD). However, the clinicopathological features, co-mutation landscape, and therapeutic outcomes across different RET fusion partners remain incompletely characterized. Methods: We retrospectively analyzed 268 patients with RET fusion–positive LUAD diagnosed between July 2017 and December 2024. Clinicopathological characteristics, metastatic patterns, and concomitant mutations were compared between KIF5B and non- KIF5B subgroups. Treatment outcomes of selective RET inhibitors, multikinase inhibitors (MKIs), and immunotherapy combined with chemotherapy were assessed, with subgroup analyses according to RET fusion partners. Results: The median age at diagnosis was 58 years, and most patients were female (57.0%) and never/light smokers (60.8%). Bone (12.3%), pleural (11.9%), and brain metastases (6.7%) were the most common metastatic sites. KIF5B-RET fusions were more frequently detected in earlier disease stages compared with non- KIF5B fusions (p = 0.0531). Among 274 RET fusion events, KIF5B-RET was predominant (65%), followed by CCDC6-RET (16%) and NCOA4-RET (1%). Concomitant mutations were identified in 28.7% of patients, most commonly TP53 (39.0%) and CDKN2A (13.0%), with CDKN2A more enriched in the non- KIF5B group (p = 0.0393). Nineteen patients received targeted therapy, including pralsetinib (n=12), selpercatinib (n=2), and cabozantinib (n=5), achieving an overall ORR of 57.9% and median PFS of 12.0 months. Notably, non- KIF5B patients demonstrated longer median PFS than KIF5B patients under pralsetinib (17.0 vs. 5.5 months, p = 0.0473). Fifteen patients received first-line immunochemotherapy, achieving a median PFS of 17.0 months, ORR of 40.0%, and DCR of 80.0%, comparable to targeted therapy (p = 0.3871). PD-L1 expression showed no correlation with outcomes. Conclusions: RET fusion–positive LUAD comprises biologically heterogeneous subsets defined by fusion partners. KIF5B-RET fusions tend to occur at earlier stages, whereas non- KIF5B fusions are more frequently associated with CDKN2A co-mutations and appear to derive greater benefit from selective RET inhibition. Immunochemotherapy demonstrates comparable efficacy regardless of fusion partner, highlighting the need for partner-specific therapeutic strategies in RET fusion–positive LUAD.
Five-year outcomes of osimertinib-based treatment in a phase III study comparing EGFR tyrosine kinase inhibitor (EGFR-TKI) monotherapy and EGFR-TKI with inserted cisplatin plus pemetrexed as a first-line treatment for advanced non-squamous non–small-cell lung cancer harboring <i>EGFR</i> mutation (JCOG1404/WJOG8214L).
8649 Background: JCOG1404/WJOG8214L was an open label, multicenter, randomized phase III study comparing EGFR-TKI monotherapy (gefitinib [Gef] or osimertinib [Osi]) and EGFR-TKI with inserted cisplatin plus pemetrexed as a first-line treatment for advanced non-squamous non–small-cell lung cancer harboring EGFR mutation ( EGFR -NSqNSCLC). In the primary analysis, the insertion of platinum-doublet chemotherapy after the initial response to EGFR-TKI could improve progression-free survival (PFS), but not overall survival (OS) compared with EGFR-TKI monotherapy (Clin Cancer Res 2025;31:2317-26). This study was commenced using Gef in December 2015 and was switched to Osi in October 2018. 501 patients (pts) (308 in the Gef cohort, 193 in the Osi cohort) were enrolled to October 2020, but it resulted in later accrual and shorter follow-up for the Osi cohort at the time of the primary analysis (data cutoff November 2022; median follow-up of all randomized patients 36.0 months). Therefore, we conducted the five-year (5y) follow-up analysis of the Osi cohort. Methods: The key eligibility criteria were pts with advanced or recurrent EGFR -NSqNSCLC (exon 19 deletion or exon21 L858R), age 20 to 74 years, and PS 0 or 1. In the standard arm (SA), Gef or Osi was administrated until disease progression. In the experimental arm (EA), Gef or Osi was administered on days 1-56. Then, after a two-week drug-free period, three cycles of cisplatin and pemetrexed were administered on days 71, 92, and 113. Thereafter, Gef or Osi was reinitiated on day 134 and continued until disease progression. Results: From October 2018 to October 2020, 193 pts were enrolled in the Osi cohort (97 pts in SA and 96 pts in EA). Median follow-up was 64.8 months. Advanced stage and recurrent disease were 79% and 21%, female and male were 63% and 37%, exon 19 deletion and exon 21 L858R were 54% and 46%, PS 0 and 1 were 50% and 50%, ≥ 65 year and < 65 year were 57% and 43%, central nerve metastasis (+) and (-) were 27% and 73%, respectively. Median OS were 54.0 months (95% confidence interval [CI] 44.4 to 66.0) in SA and 50.4 months (95% CI 43.2 to 69.6) in the EA (HR, 0.984; 95% CI, 0.684-1.415; p = 0.9279). 5y OS were 43.9% and 40.4%, respectively. Median PFS were 20.4 months (95% CI 14.4 to 28.8) in SA and 25.2 months (95% CI 18.0 to 33.6) in EA (HR, 0.902; 95% CI, 0.663-1.227; p = 0.5147). 5y PFS were 14.3% and 16.3%, respectively. Conclusions: The insertion of platinum-doublet chemotherapy after the initial response to Osi could not improve PFS and OS of pts with advanced EGFR -NSqNSCLC. On the other hand, JCOG1404/WJOG8214L demonstrated that Osi-based first-line treatment achieved 5y PFS in approximately 15% of this population, providing a benchmark for emerging Osi-based strategies. Clinical trial information: UMIN000020242.
In-hospital complications and outcomes of autologous stem cell transplantation in diffuse large B-cell lymphoma with and without chronic kidney disease.
e19109 Background: Chronic kidney disease (CKD) may increase transplant-related toxicity during autologous stem cell transplantation (autoSCT) for diffuse large B-cell lymphoma (DLBCL). Contemporary national inpatient outcomes data for this subgroup are limited. Methods: We performed a retrospective cohort study using the 2022 National Inpatient Sample (NIS), which includes ~20% of U.S. hospital discharges. Adults (≥18 years) hospitalized with DLBCL who underwent bone marrow transplant/autoSCT were identified using ICD-10-CM/PCS codes and stratified by secondary diagnosis of CKD. Multivariable logistic regression was used for categorical outcomes and linear regression for continuous outcomes (length of stay [LOS], total hospitalization charges), adjusting for age, sex, race, Elixhauser comorbidity score, insurance status, and hospital characteristics. Results: We identified 1,025 DLBCL autoSCT hospitalizations; 80 (7.8%) had CKD. Mean age was 59.8 vs 58.6 years (p=0.63) and 68.8% vs 52.4% were male (p=0.21) in the CKD vs non-CKD cohorts. CKD was independently associated with higher AKI (56.25% vs 11.11%; adjusted OR [aOR] 8.48, 95% CI 1.88–38.1; p=0.005). Differences were not statistically significant for AKI requiring HD (6.25% vs 1.59%; aOR 4.76, 95% CI 0.41–55.2; p=0.21), septic shock (6.25% vs 3.70%; aOR 3.92, 95% CI 0.44–34.9; p=0.22), in-hospital mortality (6.25% vs 4.23%; aOR 1.41, 95% CI 0.20–9.7; p=0.72), or intubation (6.25% vs 1.40%; aOR 0.32, 95% CI 0.04–2.07; p=0.23). Mean total charges were $100,488 lower and mean LOS 2.9 days shorter in the CKD cohort versus non-CKD; however, neither difference was statistically significant. Conclusions: In a national inpatient cohort of DLBCL hospitalizations undergoing autoSCT, pre-existing CKD was independently associated with a markedly higher risk of AKI, highlighting renal vulnerability during transplant admission. In contrast, differences in AKI requiring HD, septic shock, intubation, LOS, charges, and in-hospital mortality were not statistically significant after adjustment. Taken together, these findings emphasize the need for heightened vigilance for AKI in high-risk patients with CKD. It supports proactive peri-transplant renal risk mitigation, including optimizing fluid management and medication review to minimize AKI development.
Thyroid cancer risk in systemic lupus erythematosus: A population-based retrospective cohort study.
e18043 Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease marked by immune dysregulation and long-standing inflammation, factors that may contribute to an increased risk of malignancy. Although SLE has been linked to several cancers, population-level data specifically examining the risk of thyroid cancer in patients with SLE remain limited. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health record database comprising multiple international healthcare organizations. Adults aged 18–49 years between January 1, 2015, and December 31, 2025, were included. Patients with SLE were identified using the ICD-10 code M32, with the earliest recorded diagnosis serving as the index date. A comparator cohort without any recorded diagnosis of SLE was constructed from the same network. Patients with a history of thyroid cancer before cohort entry were excluded to ensure assessment of incident disease. The primary outcome was incident thyroid cancer, identified using ICD-O-3 code C73. Incidence proportions and incidence rates (cases per person-day) were calculated and stratified by age, sex, race, and ethnicity. Results: The analysis included 102,072 patients with SLE and 34,755,380 patients without SLE. Patients with SLE had a substantially higher incidence of thyroid cancer than those without SLE. The incidence proportion of thyroid cancer was 0.000098 in the SLE cohort compared with 0.00000471 in the non-SLE cohort, corresponding to an approximately 20-fold higher incidence among patients with SLE. The incidence rates were 0.0000000431 and 0.00000000377 cases per person-day, respectively. Thyroid cancer occurred almost exclusively among female patients in both cohorts, with the highest incidence observed in females with SLE. Age-stratified analyses showed that the excess risk in the SLE cohort was most pronounced among patients aged 25–39 years, while incidence remained consistently low across all age groups in the non-SLE cohort. Conclusions: In this large real-world cohort, systemic lupus erythematosus was associated with a markedly increased incidence of thyroid cancer, particularly among young and middle-aged women. These findings support a potential link between systemic autoimmunity and thyroid carcinogenesis and underscore the need for future adjusted analyses to better define underlying mechanisms and clinical implications.
Trends, outcomes, and disparities in lung cancer–related hospitalizations in the United States: 2012–2022.
e20112 Background: Lung Cancer remains a leading cause of morbidity and mortality in the United States and accounts for significant inpatient and emergency department services utilization. Advances in Lung Cancer treatment have resulted in improvement of survival after diagnosis. However, the impact on inpatient services utilization and inpatient outcomes remains unclear. Methods: We performed a retrospective analysis of lung cancer-related hospitalizations (LCHs) using the National Inpatient Sample from 2012 to 2022. LCHs were identified using ICD-9 and ICD-10 diagnosis codes. Hospitalization rates were calculated per 100,000 U.S. population and analyzed over time using Poisson regression. The primary outcome was in-hospital mortality (IHM). Secondary outcomes included length of stay, hospitalization costs, discharge disposition, and primary non-cancer reason for hospitalization. Univariate and multivariate logistic regression were used to identify factors associated with IHM. Results: A total of 4,399,594 LCH were identified from 2012-2022. The median age was 69 years (IQR 62–77), and 51.3% of hospitalizations occurred among males. Overall LCHs rates increased modestly over time (IRR 1.01; 95% CI 1.00–1.01; p < 0.001) relative to general hospitalizations, with a notable decrease in 2020, resembling declines in general hospitalizations during this period. IHM rates had shown a tendency to decline prior to 2020 (IRR = 0.99; p < 0.001; 95% CI = 0.98-0.99), with a steady increase in subsequent years (p < 0.001; IRR = 1.05; 95% CI = 1.04-1.06) Mortality rates were higher among males, Asian/Pacific Islanders, Native Americans, and Hispanics. Median length of stay was 4 days (IQR 3–8). Median hospitalization cost was $42,983 (IQR $22,437–$80,557), with higher costs among Hispanics and Asian/Pacific Islanders. In adjusted analyses, increasing age (aOR 1.02 per decade), male sex (aOR 0.81 for females), Asian/Pacific Islander ethnicity (aOR 1.10), cirrhosis (aOR 1.57), and chronic kidney disease (aOR 1.16) were independently associated with increased IHM (p < 0.001). Treatment at urban teaching hospitals (aOR 0.91) was associated with reduced IHM (p < 0.001). Conclusions: During a decade marked by major therapeutic breakthroughs, LCH rates increased modestly. Despite a prepandemic decline, IHM has recently shown a steady increase. Length of stay and hospitalization costs remain substantial, with persistent disparities across demographic and clinical subgroups. Despite improvements in lung cancer patients' survival, the inpatient burden of lung cancer seems to be increasing. Targeted efforts to optimize inpatient management, address comorbidity burden, and reduce structural inequities are needed to further improve outcomes in the modern treatment era.
Bridging gaps in relapsed/refractory follicular lymphoma care: Perceived barriers to treatment and clinical trial access.
e13547 Background: Despite expanding therapeutic options and clinical guidelines for relapsed/refractory follicular lymphoma (R/R FL), optimal care delivery remains challenging due to complex treatment decisions and system-level barriers. This study explored perceived barriers and facilitators to R/R FL care and clinical trial access from both provider and patient perspectives. Methods: Using an explanatory sequential mixed-methods approach, the Association of Cancer Care Centers (ACCC), in partnership with patient advocacy organizations, convened an expert advisory committee to support study design. Two focus groups and 6 key informant interviews were conducted May-June 2025. One focus group and 2 interviews included patients with R/R FL, caregivers, and patient advocacy representativesother focus group and remaining interviews included multidisciplinary healthcare professionals (HCP) involved in R/R FL care in the U.S. Qualitative data were stratified by stakeholder group and analyzed thematically. Results: Focus group participants (n = 25) included HCPs (n = 12), patients (n = 8), advocacy representatives (n = 3) and caregivers (n = 2). Interviews included HCPs (n = 4) and patients (n = 2). Providers prioritized individualized treatment sequencing, assessment for transformation, and use of newer therapies when feasible. Clinical trials were viewed as important but limited by geography, health literacy, and eligibility criteria, with variability in when trials were introduced across treatment lines. Insurance and geographic barriers were cited as the most common challenges to timely, guideline-concordant care. Providers emphasized shared decision-making (SDM), patient education, and coordination between community and tertiary centers as best practices. Yet, patients perceived varying degrees of SDM. Some patients felt empowered to make decisions while others received limited options. Emotional support was inconsistently addressed, often absent unless patients or caregivers sought it out. Regarding clinical trials, participants noted limited targeted information for refractory disease and inequitable access to trials and specialty centers, though some overcame barriers through self-advocacy and persistence. Patients identified key supports for informed SDM, including trusting provider relationships, access to accurate information, and engagement with patient advocacy organizations for peer support. Conclusions: Although providers emphasized SDM as central to R/R FL care, patient experiences revealed inconsistent implementation in practice. This disconnect highlights the need for intentional strategies to operationalize SDM across care settings, including improved communication, patient education, and structural supports to ensure patient values meaningfully inform treatment and clinical trial decisions.
Bladder preservation in patients with urothelial muscle-invasive bladder cancer who refused radical cystectomy after clinical complete response to trans-urethral resection of bladder tumors and neoadjuvant systemic chemotherapy. A retrospective single-center experience.
e16585 Background: Neoadjuvant systemic chemotherapy (NASCT) followed by radical cystectomy (RC) is widely used among the standard treatments for patients with muscle invasive bladder cancer (MIBC). RC is associated with significant morbidity and worsening of quality of life. We conducted a retrospective single-center analyses including patients with non-metastatic urothelial MIBC who refused RC after the achievement of clinical complete response to trans-urethral resection of bladder tumor (TURBT) and NASCT. Methods: Before NASCT, patients uderwent complete initial TURBT, and 4-5 weeks later to maximal restaging TURBT, random cold-cup biopsies of the bladder and prostatic urethra, and urinary cytology.. Patients with concomitant carcinoma in situ, tumors of the upper urinary tract or prostatic urethra, hydronephrosis and reduced bladder capacity were referred for RC. After NASCT patients were managed with intravesical sequential BCG and Mitomycin to prevent disease recurrence. Patients were assessed with urinary cytology, cystoscopy and imaging at 3 month intervals for 2 years, 6 month interval for 3 years and yearly thereafter. The primary endpoint was the event-free survival (EFS), defined as the absence of urothelial high grade tumor relapse or cancer-specific death . The secondary endpoints were bladder preservation rate and the overall survival (OS). Results: From July 1997 to December 2021, 237 patients with MIBC (cT2/3 - cN0 - cM0), received TURBT, restaging TURBT and platinum based NASCT (gemcitabine plus cisplatin [n = 179]; dose-dense MVAC [n = 58] with evidence of complete clinical response (pT0-Nx-MX) ; among these 159 refused RC. The median age was 57yo and 84.9% were male. All patients received susequent intravesical sequential BCG and Mitomycin. After a medial follow-up of 15.1 years, 129 (81.1%) patients had an EFS. Twenty-six patients (16.3%) had a new MIBC occurred in the bladder (n = 7), urethra (n = 6) and upper urinary tract (3 = 13); 6 patients developed distant metastases and died. The stimated 10-yr EFS and OS were 81.4% (95% CI: 74.9-88.5) AND 85.2% (95% CI: 79.2-91.6), respectively. The 10-yr bladder preservation rate was 94.5% (95 CI: 90.5-98.6). In multivariable analyses, older age, multifocal disease, and tumor larger than 5 cm were significantly associated with worse EFS (HR = 1.06, p = 0.004) and OS (HR = 1.1, p < 0.001). Conclusions: In this retrospective MIBC cohort, selected patients who refused RC had benefit from multimodal approach including maximal TURBT, NESCTand intravesical sequential ommuno-chemo-therapy to prevent disease recurrence. These results deserve future investigations in prospective bladder-sparing trials.
Evaluation of circulating tumor DNA (ctDNA) following liver resection in a high-risk population with colorectal liver metastases.
3556 Background: Liver resection is routinely performed for oligometastatic colorectal cancer (CRC). ctDNA analysis is becoming important in the management of primary CRC following surgery, but in patients with liver metastases, its role is less clear. This study aimed to evaluate the performance of a plasma ctDNA assay for early detection of recurrence in patients with liver only CRC metastases post surgical resection. The cohort included patients who had inoperable disease prior to induction chemotherapy and those having repeat resections. Patients with the primary cancer in situ were included if a synchronous resection was performed. Methods: 61 patients (42 male, median age 68 [range 41-85]) were studied. All patients had CRC liver metastases as the sole metastatic site on evaluation by CT and MRI. Patients were followed up clinically with regular CT imaging. Plasma samples were collected at baseline (pre-surgery, n = 55) and 5 days to 1+ year after surgery, and were tested retrospectively on a blood-only, tumor-agnostic, targeted methylation assay that interrogates informative methylation regions for signal indicative of ctDNA using a machine learning classifier (GRAIL, Inc., Menlo Park, CA). Results: ctDNA was detected in 94.5% (52/55) of patients at the pre-surgery timepoint. During clinical surveillance, 46 developed recurrence, 5 had no recurrence for at least 2 years after surgery, and 10 had follow-up for less than 2 years. Among patients with recurrence, ctDNA was detected in 80.4% (37/46) of patients before recurrence, with a median lead time of 245 days [IQR: 65 - 393 days]. All five patients who remained recurrence-free for at least 2 years had undetectable ctDNA following surgery. ctDNA was detected in 57.8% (26/45) of patients who recurred and had plasma collected within 3 months following surgery. Recurrence-free survival (RFS) was significantly lower in patients with ctDNA detected within 3 months after surgery (median RFS 272 vs. 593 days, log-rank p-value < 0.01). Conclusions: ctDNA analysis using a methylation-based assay allowed the detection of minimal residual disease and the prediction of recurrence in many patients following resection of CRC liver metastases. These data support the potential use of this biomarker for patient management pending confirmation in prospective clinical studies.
Risk factors in association with adrenal insufficiency in hospitalized solid tumor patients on immunotherapy.
e24183 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy and significantly improved clinical outcomes. However, their use has been associated with immune-related adverse events (irAEs). Among these, primary adrenal insufficiency is an uncommon but potentially life-threatening complication that carries a substantial risk of morbidity and mortality as it can lead to shock. The objective of the study was to identify risk factors associated with the development of immunotherapy related (IR) adrenal insufficiency. Methods: We conducted a retrospective chart review of solid-tumor patients admitted to the hospital medicine service for IR toxicities between 2021 and 2022, to identify cases of IR adrenal insufficiency. Patient demographics and baseline characteristics were analyzed by descriptive statistics. Logistic regression analysis was used to assess the association between baseline characteristics and the relative risk of developing IR adrenal insufficiency. Results: Over the study period, 144 patients required hospitalization for complications attributed to IR toxicities. Among these, 10 patients (7%) were found to have adrenal insufficiency. Patient demographics and baseline characteristics are shown in Table 1. After logistic regression univariate analysis, characteristics associated with the risk of developing IR adrenal insufficiency included: Use of Ipilimumab (OR:12.53 , CI 3.41–46.01 p = 0.001), Use of Nivolumab (OR : 7.30, CI 1.85 – 28.74 p = 0.004 ), Immunotherapy type Anti CTLA-4 with Anti PD-1 (OR: 7.84 CI 2.11– 29.17 p = 0.002 ) and Anti CTLA-4 alone (OR: 11.44 CI 2.12– 61.67 p = 0.005 ). A trend toward an association was observed for history of Stroke (OR: 3.9, CI 0.79-19.34 p = 0.096) and for cancer stage (OR: 0.57 CI 0.29-1.09, p = 0.089). Conclusions: ICI associated adrenal insufficiency was strongly associated with exposure to CTLA-4 based regimens, particularly Ipilimumab alone and in combination with Anti PD-1. These findings suggest a distinct high-risk population warranting heightened vigilance. Awareness of baseline and treatment-related risk factors may facilitate earlier diagnosis and mitigate morbidity and mortality associated with this IR endocrinopathy. Further studies are needed to corroborate these findings. CHARACTERISTIC OVERALL (N=10) GENDER, n (%)FemaleMale 4 (40%)6 (60%) RACE, n (%) Asian Black or African American Other White or Caucasian 1 (10.00%) 0 (0%) 1 (10.00%) 8 (80%) CANCER STAGE, n (%) Stage I Stage IV Unknown 2 (20%) 7 (70%) 1 (10%) HYPERTENSION, n (%) NO YES 6 (60%) 4 (40%) DIABETES, n (%) NO YES 7 (70%) 3 (30%) IMMUNOTHERAPY, n (%) Ipilimumab Pembrolizumab Nivolumab Atezolizumab 6 (60%) 2 (20%) 7 (70%) 2 (20%) IMMUNOTHERAPY TYPE, n (%)ANTI PD-1 ANTI PD-L1 ANTI PD-1 / ANTI PD-L1 ANTI CTLA-4 ANTI CTLA-4 WITH ANTI PD-1 4 (40%) 1 (10%) 1 (10%) 2 (20%) 4 (40%) CANCER TYPE Head and Neck Lung and Thorax GI 3 (30%) 3 (30%) 4 (40%)
Burden of early-onset cancers in Hungary: Nationwide trends in incidence and mortality.
e22616 Background: Cancers diagnosed before 50 years of age (“early-onset” cancers) are increasingly recognized as a distinct epidemiologic and clinical entity. However, population-level data describing their contribution to cancer burden in Central and Eastern Europe remain limited. We evaluated the incidence and mortality of major early-onset cancers in Hungary using nationwide administrative data. Methods: We analyzed nationwide oncology records from the Hungarian National Health Insurance Fund (NEAK), covering the entire population, for major cancer types including colorectal (C18), breast (C50), lung (C34), testicular (C62), melanoma (C43), and gastric (C16) cancers. Annual incidence, mortality, and prevalence were calculated using national population denominators. Analyses were stratified by sex, cancer type, and early-onset status (diagnosis < 50 years). Temporal patterns were assessed by comparing earlier baseline periods with more recent years, and findings were cross-validated against publicly available national cancer registry statistics. Results: Early-onset cancers constituted a substantial proportion of incident cases, with marked heterogeneity across tumor types. Among newly diagnosed cases, cancers diagnosed before age 50 accounted for 18.9% of breast cancer, 74.9% of testicular cancer, 22.7% of melanoma, 3.6% of lung cancer, and 6.3% of gastric cancer. Early-onset disease also contributed meaningfully to cancer-related mortality: 5.7% of breast cancer deaths, 32.0% of testicular cancer deaths, 4.8% of melanoma deaths, 2.0% of lung cancer deaths, and 4.3% of gastric cancer deaths occurred in patients younger than 50 years. Trends over time demonstrated variable patterns by cancer type, indicating differential contributions of early-onset disease to national cancer burden. Conclusions: Nationwide administrative data from Hungary demonstrate that cancers diagnosed before age 50 contribute a non-negligible proportion of both incident cases and cancer-related deaths across multiple tumor types. The observed heterogeneity underscores the need for tumor-specific evaluation of early-onset cancer trends and supports further investigation into tailored prevention, screening, and survivorship strategies for younger populations.
Real-world outcomes of mogamulizumab retreatment in cutaneous T-cell lymphoma: A single-center retrospective study.
7096 Background: Mogamulizumab, monoclonal antibody against CCR4, is approved for relapsed/refractory cutaneous T cell lymphoma (CTCL), with an overall response rate of 28%in CTCL. The most common toxicity is mogamulizumab-associated rash (MAR), occurring in ~24% of patients and reported in up to 88% of responders, frequently leading to treatment discontinuation. Given the limited therapeutic options in CTCL, retreatment with mogamulizumab is clinically appealing but not well described. We report a single center experience with mogamulizumab retreatment in patients with CTCL. Methods: We conducted a single-center retrospective study of all adult patients with CTCL treated with mogamulizumab from 2013 to 2025. Retreatment was defined as reinitiation after a >90-day treatment-free interval. Disease status, patient characteristics, response and toxicity to therapy was collected. Results: Among 54 CTCL patients treated with mogamulizumab, 13 (24%) (MF=7, SS=6) underwent retreatment. Median age at diagnosis was 67 years (range, 44 - 84) and mostly male (69%). Patients had a median of 5 prior systemic therapy lines (range, 3–9). The median interval from initial mogamulizumab discontinuation to retreatment was 11.4 months (range 3.1- 40.2). During initial mogamulizumab exposure, ORR 92.3% (12/13, 8 CR, 4 PR).11 discontinued mogamulizumab due to rash, 1 due to clinical response and 1 with PD. Retreatment dosing schedules included weekly administration in 2 patients (15%), every-2-week dosing in 8 (62%), and every-4-week dosing in 3 (23%). On retreatment, ORR was 38.5% (5/13) with CR in 2 patients and PR in 3, SD in 3 and progressive disease (PD) in 5. Median number of doses on retreatment was 5 (range 1-44). Among retreatment responders (CR/PR; n=5), median DOR was 15.0 months (range, 6.2–28.0). Median PFS from retreatment initiation was 4.0 months (range, 0.0–40.7) and estimated 2 -year OS was 84.6%. Both deaths were unrelated to CTCL progression or mogamulizumab-related toxicity. MAR occurred in 10/13 (76.9%) patients on retreatment. Rechallenge strategies included temporary treatment interruption until resolution of MAR (n=7) and increasing dosing intervals (n=3). Rash was predominantly maculopapular or morbilliform, most commonly involving the trunk and extremities. All MAR events were CTCAE grade 1-2. MAR was managed with topical steroids (n=9), oral steroids (n=1), and cessation of mogamulizumab (n=9). Conclusions: In this real-world, heavily pretreated CTCL cohort, mogamulizumab retreatment demonstrated meaningful clinical activity with durable responses in patients despite prior exposure. Although rash was common, it was most often low to moderate grade, responsive to standard management, and retreatment or rechallenge after resolution was feasible.
Delayed cation dynamics enables dual-doped organic electrochemical transistors with high current sensitivity
Abstract The coupling between ionic and electronic species and their dynamic interplay lay the foundation for organic electrochemical transistors (OECTs) to transduce and amplify bio(chemical) signals through ion-modulated conductivity. However, the operation of most reported OECTs is typically dominated by single ions, e.g. anions for p-type accumulation devices, mainly due to the challenge of regulating ion dynamics to enable both types of ions to play a role during the electrochemical doping process. In this study, we propose that electrochemical doping of an OECT channel can occur via an anion-cation dual-doping mechanism, where cation expulsion and anion injection occur simultaneously. By designing a p-type organic mixed ionic-electronic conductor, Pu2gT, with strong side chain-cation interactions, we successfully decelerate the cation transport dynamics, allowing the dual-doping process to occur. As a result, Pu2gT OECT exhibits improved current sensitivity compared with the anion-dominated counterpart, showing potential in high-quality electrocardiogram signal acquisition and ion concentration discrimination. Furthermore, incorporating crown ether additives into Pu2gT enhances the dual-doping effect by further delaying cation dynamics, leading to even higher device performance. This dual-doping mechanism deepens the understanding of OECT working principles and opens avenues for achieving state-of-the-art bioelectronic devices.
Feasibility study of prolonged administration of naxitamab, irinotecan, and temozolomide for patients with relapsed or refractory neuroblastoma.
TPS10058 Background: Neuroblastoma is a malignant childhood tumor of the sympathetic nervous system. Cure rates are unsatisfactory for patients with high-risk disease (approximate 3-year EFS 50%) with current standard of care therapy. For patients who relapsed, anti-GD2 based chemoimmunotherapy has become standard, though it often requires in-hospital administration. Naxitamab, a humanized anti-GD2 monoclonal antibody (mAb), is FDA approved for patients with relapsed or refractory (R/R) high-risk neuroblastoma (HR-NB) with metastatic disease restricted to bone or bone marrow (BM), and who have stable disease or minor/partial response to previous therapies. With an infusion duration of 30-60 minutes, grade 3 pain and infusion-related reactions are common (72% and 68% of patients respectively) and necessitate extensive nursing and provider resources that may preclude administration at many centers. Slowing the rate of infusion of naxitamab and other anti-GD2 mAbs is generally associated with lower rates and severity of acute toxicity. We have therefore opened a phase I feasibility trial of prolonged administration of naxitamab in combination with irinotecan and temozolomide. Methods: This is a phase 1, single treatment arm, modified 3+3 prospective trial in patients with R/R or progressive HR-NB. The primary objective is to identify a recommended safe and feasible prolonged infusion duration of naxitamab in combination with irinotecan and temozolomide, with a goal of still allowing outpatient administration. Patients are enrolled at the starting total infusion duration of 4 hours, with an escalating infusion rate at pre-defined timepoints; the total infusion duration will be extended or shortened in cohorts of 3-6 patients based on safety and adverse events (AEs) observed in the first cycle. Individual patients will be eligible for duration escalation or de-escalation depending on AEs observed. An expansion cohort will be enrolled at the recommended infusion time. Key eligibility criteria include diagnosis of R/R or progressive HR-NB or ganglioneuroblastoma, age 1-30 years at enrollment, documentation of disease per revised International Neuroblastoma Response Criteria (INRC), adequate performance level, and adequate organ function including BM. Key exclusion criteria include prior receipt of naxitamab, untreated CNS metastatic disease, and discontinuation of prior GD2 immunotherapy due to unacceptable toxicity other than allergic reaction. Secondary endpoints include response rate per revised INRC and survival outcomes. Correlative and exploratory investigations embedded within the trial include PK profiling of prolonged naxitamab infusion durations and evaluation of circulating biomarkers including circulating tumor DNA, tumor cells, and GD2 in the study population during anti-GD2 therapy. Clinical trial information: NCT07027748 .
Shifting patterns in PMBCL and DLBCL care: The role of community oncology centers in the U.S.
e19071 Background: Historically, clinical trials and adoption of novel therapies for oncology have been concentrated within academic centers, which are associated with better research infrastructure and specialized expertise. However, this juxtaposes current care patterns, as many patients receive treatment in community centers. This analysis aimed to determine where patients are treated, prescribed CAR-T and bispecific therapies today and to characterize referral pathways between community and academic centers. Methods: 23,143 incident-treated patients with diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) were identified in a U.S. Komodo open and closed claims database between July 2023 and June 2025. Patients were mapped to 18,666 hematologist and/or oncologist treaters, who in turn were mapped to their primary affiliation using Definitive Healthcare affiliations. Treaters were mapped to 191 out of 217 academic medical centers in the US and 2,297 community centers. Results: A total of 70% of patients were treated exclusively in community centers, 23% exclusively in academic centers, and 7% received care in both settings over the study period. On average, community centers treated 10 patients, and academic centers treated 38 patients. Among centers with evidence of CAR-T and bispecific treatment capabilities, averages increased to 33 patients at community centers and 62 patients at academic centers. Within two years of diagnosis, 3% of patients received CAR-T therapy, 43% of whom received it in a community center. Bispecific antibody therapies were received by 2% of patients, of whom 50% received it in a community center. Overall, only 16% of patients had a referral to another center, of which a minority of referrals were to academic centers. Among patients who were treated with CAR-T or bispecific therapies, referral patterns shifted even further toward community centers: only 11% of patients treated with CAR-T and 13% of patients treated with bispecific therapy were referred to an academic center for treatment. Conclusions: In this national cohort, most patients with DLBCL/PMBCL received care exclusively in community centers, with advanced therapies such as CAR-T and bispecific antibodies delivered across both community and academic settings. Inter-center referrals were uncommon, and referrals to academic centers were particularly limited among patients receiving advanced therapies. These findings highlight the importance of including community centers with demonstrated treatment capabilities when evaluating potential sites for clinical trial recruitment.
Facility-level differences and outcomes in elderly primary CNS lymphoma in the NCDB.
e13762 Background: PCNSL is a rare, aggressive subtype of non-Hodgkin lymphoma with increasing incidence in the U.S (ACSPMID:19273630). Outcomes in older adults remain poor; prior cohorts of patients aged > 70 years reported a 2-year overall survival of 50% (NCBIPMID:32241841). Facility-level differences in care have been reported, but their impact on older adults is unclear. We compared academic vs community cancer programs in elderly PCNSL to evaluate demographic, socioeconomic, and survival differences. Methods: A retrospective cohort study of patients diagnosed with PCNSL between 2004-2022 using the National Cancer Database (NCDB) for patients ≥75 years old. Patients were classified by treatment facility: ACP (academic/research programs including NCI-designated centers) vs. CCP (community, comprehensive community, and integrated network cancer programs). Demographic, clinical, and treatment characteristics were compared using chi-square and Wilcoxon tests. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS), adjusting for age, race/ethnicity, insurance status, Charlson-Deyo comorbidity index, and distance traveled for care. Results: 5,013 patients aged ≥75 with PCNSL, 3,204 were treated at ACP and 1,809 at CCP. Median age, sex, comorbidity burden, and stage were similar across facility types. Ethnicity did not differ (p = 0.054). CCP cared for a higher proportion of lower-income patients (2016–2020: 15% vs 10%; p < 0.001) and were more frequently located in non–Medicaid expansion states (39% vs 31%; p < 0.001), while ACP patients traveled farther (median 14.9 vs 9.2 miles; p < 0.001). Treatment at ACP were less likely to receive no treatment (6% vs 12%; p < 0.001), more likely to receive treatment (70% vs 63%; p < 0.001) and initiated systemic therapy sooner (median 15 vs 18 days; p = 0.001). Radiation was more frequently administered in CCP (24% vs 20%; p = 0.002). Early mortality was higher in CCP (30-day: 4% vs 3%, p = 0.013; 90-day: 13% vs 10%, p = 0.011). OS favored ACP, with higher 2-year (31% vs 23%), 5-year (19% vs 13%) and 10-year (9% vs 5%) survival and adjusted median survival (0.48 vs 0.32 years). Conclusions: Among patients aged ≥75 years with PCNS, OS differed significantly by treatment facility type, with a statistically and clinically meaningful survival advantage observed among patients treated at ACP compared with CCP. OS difference was consistent across short- and long-term follow-up with lower early mortality, higher rates of treatment delivery, and shorter time to initiation of therapy at ACP. These results point to system-level gaps in care for older adults with PCNSL and underscore the need to strengthen referral pathways to ACP and build structured academic–community partnerships. Doing so could expand timely access to specialized multidisciplinary care and clinical trials for vulnerable patients more often treated in lower-resource settings.
Assessing current sleep–cognition evidence and translation into oncology practice.
e24129 Background: Despite strong evidence linking sleep disturbance with cognitive outcomes in cancer survivors, oncology practice lacks a standardized framework defining how sleep should be integrated into cognitive evaluation and management. The aim of this integrative review was to describe how sleep and cognition have been conceptualized and measured in existing studies and to examine the extent to which current approaches support or limit clinical interpretability and translation. Methods: We conducted an integrative review following Whittemore and Knafl methodology. A comprehensive search was performed in Embase, Web of Science, Ovid MEDLINE, PubMed, and CINAHL for studies published between 2016 and April 2025. Eligible studies included empirical data on both sleep and cognitive outcomes in cancer survivors. After systematic screening, 37 studies were included. Data extraction captured study design, population characteristics, cancer type and treatment exposures, sleep and cognitive measurement tools, analytic approaches, and reported associations. Sleep and cognitive outcomes were synthesized exactly as operationalized in the original studies, preserving their reported constructs and metrics, to evaluate the scope, consistency, and clinical interpretability of existing evidence. Results: Across 37 studies including 18,509 cancer survivors, sleep and cognition were conceptualized and measured using highly variable and largely non-standardized approaches. Nearly half of studies were cross-sectional (46%), limiting temporal or clinical inference. Sleep assessment relied predominantly on self-report instruments (89%), most often PSQI or ISI, with only 11% incorporating objective measures. In most studies, sleep was reported as a single global score rather than as distinct dimensions. Cognitive outcomes were similarly heterogeneous. More than two-thirds of studies used self-reported cognition, while only about half included performance-based testing, with inconsistent selection of cognitive domains and limited standardization of outcome definitions. Because sleep was rarely characterized by dimension and cognition was inconsistently assessed by domain, most studies reported broad sleep–cognition associations without providing clinically interpretable guidance on which sleep characteristics should be evaluated, which cognitive outcomes they relate to, or how findings could inform clinical decision making. Conclusions: Sleep–cognition evidence has not translated into oncology practice because of heterogeneous measurements, largely non-standardized approaches that do not specify which sleep dimensions relate to which cognitive domains. Without dimensional sleep assessment and domain-specific cognitive evaluation, findings remain descriptive rather than clinically actionable. Standardized frameworks are needed to enable meaningful clinical integration.
Prevalence of oral and genital HPV-45 and non–vaccine-targeted HPV-35 among U.S. adults.
10597 Background: High-risk human papillomavirus (HPV) types 35 and 45 are oncogenic non-16/18 subtypes that contribute measurably to HPV-attributable genital and oropharyngeal cancers. Unlike HPV-45, HPV-35 is not targeted by the current 9-valent vaccine. Although high prevalence of these subtypes has been reported in some global sub-populations, data on their prevalence and distribution in the U.S. adult population remains limited. Methods: We conducted a cross-sectional analysis of adults aged 18-64 years from the National Health and Nutrition Examination Survey (NHANES) cycles 2013-2016. HPV was detected via self-collected oral rinse specimens, vaginal swabs, and penile swabs. HPV vaccination history and sexual behaviors were self-reported. We estimated survey-weighted type-specific HPV prevalence and used survey-weighted Poisson regression to calculate adjusted prevalence ratios (aPRs), accounting for age, sex, race/ethnicity, vaccination status, and number of lifetime sexual partners. Results: Oral HPV prevalence was low overall, with HPV-16 remaining the most frequently detected type (0.87%). Genital HPV showed a broader distribution of oncogenic types. Among men, penile HPV-35 (1.93%, 95% CI 1.27-2.60%) and HPV-45 (1.94%, 95% CI 1.37-2.50%) were less prevalent than HPV-16 (3.97%, 95% CI 3.13-4.80%) and slightly more prevalent than HPV-18 (1.71%, 95% CI 1.20-2.22%), though confidence intervals overlapped. Among women, vaginal HPV-35 (1.40%, 95% CI 0.95-1.85%) and HPV-45 (1.71%, 95% CI 1.21-2.21%) were also less common than HPV-16 (2.95%, 95% CI 2.14-3.77%) and comparable to HPV-18 (1.26%, 95% CI 0.88-1.65%), again with overlapping confidence intervals. While there were extremely low rates of dual oral-genital infections, males exhibited slightly higher, though non-significant, dual infection prevalences for HPV-35 (0.03% vs. 0%), HPV-45 (0.21% vs 0.07%), and HPV-16 (0.17% vs. 0.11%) compared to females. Non-Hispanic Black participants had a significantly higher genital prevalence of both HPV-35 (aPR 2.75, 95% CI 1.71-4.42) and HPV-45 (aPR 2.08, 95% CI 1.13-3.85) compared with Non-Hispanic White participants. Prevalence was higher among males than females for both types, although these differences did not reach statistical significance. Conclusions: In this nationally representative sample of U.S. adults, we found that HPV-35, a high-risk type not included in the current 9-valent vaccine, showed genital prevalence comparable to vaccine-covered types and marked racial disparities. These findings highlight the importance of continued HPV surveillance and targeted prevention strategies. Additionally, future studies should investigate these subtypes in HPV-associated malignancies.