Citations

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children, including sensorineural hearing loss. There is interest in developing a pre-conception vaccine that could confer protective immunity on a woman of child-bearing age, hence resulting in a reduced cCMV disease burden. Other populations, including solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients, could also benefit from CMV vaccination. To review and discuss vaccines that are in clinical development, a workshop, sponsored by the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), was empaneled. At this workshop, correlates of protective immunity against CMV, epidemiologic features of CMV transmission, and vaccine platforms in development were reviewed. Representatives from academia, pharma, and the NIH engaged in discussion on the current state-of-the-art in CMV vaccinology. A summary of the presentations from this is provided in this report.

BACKGROUND AND OBJECTIVE There is limited research on screening for social determinants of health (SDOH) in hospitalized pediatric patients. In this article, we describe patient characteristics related to SDOH screening in the hospital setting and examine relationships with acute care metrics. METHODS This is a retrospective cohort study. From July 2020 to October 2021, a 14-question SDOH screener was administered to families of patients admitted or transferred to the hospital medicine service. Information was collected regarding screen results, demographics, patient comorbidities, patient complexity, and acute care metrics. Unadjusted and multivariable analyses were performed using generalized estimation equation logistic regression models. RESULTS Families in 2454 (65%) patient encounters completed SDOH screening, with ≥1 need identified in 662 (27%) encounters. Families with significant odds for positive screening results in a multivariable analysis included primary language other than English (odds ratio [OR] 4.269, confidence interval [CI] 1.731–10.533) or Spanish (OR 1.419, CI 1.050–1.918), families identifying as “Black” (OR 1.675, CI 1.237–2.266) or Hispanic (OR 1.347, CI 1.057–1.717) or having a child on the complex care registry (OR 1.466, CI 1.120–1.918). A positive screening result was not associated with increased length of stay, readmission, or 2-year emergency department or acute care utilization. CONCLUSIONS In hospitalized pediatric patients, populations at the greatest odds for positive needs include families with primary languages other than English or Spanish, those that identified as certain races or ethnicities, or those having a child on the complex care registry. A positive SDOH screening result in this study was not associated with an increase in length of stay, readmission, or acute care utilization.

Abstract Cancer is the leading cause of mortality within the Latino population. Projections suggest a 142% increase in cancer incidence among Latinos over the next two decades. This trend is concerning given that Latinos, the largest minority group in the United States, are expected to constitute at least 28% of the nation's populace by 2060. To address the need for enhanced comprehension of these trends and to identify equitable interventions targeting Latino health disparities, the Institute of Health Promotion Research and the Mays Cancer Center jointly established the biennial Advancing the Science of Cancer in Latinos (ASCL) Conference. The fourth ASCL Conference convened in San Antonio, TX from February 21-23, 2024. The conference objectives were twofold: 1) Examine the intersection of health equity and biological underpinnings in cancer control, prevention, and treatment; and 2) Foster collaborative initiatives among attendees aimed at addressing cancer-related health disparities within the Latino community. The 2024 conference attracted 286 participants compared to 251 attendees in 2022, encompassing guest speakers, researchers, physicians, healthcare professionals, patient advocates, researchers, and students. It comprised 23 sessions (3 keynotes, 6 plenaries, 6 breakouts, 3 general sessions, 1 special session, 1 lunch panel session) featuring insights from 51 speakers, alongside a poster session highlighting 80 research abstracts and a rapid-fire session tailored for early-career investigators. Sessions encompassed multiple topics relevant to Latino cancer research, spanning health disparities, clinical trials, survivorship, patient advocacy, climate change impacts on cancer, precision medicine, health policy and social determinants of health. A post-conference survey from a cohort of 48 respondents underscored high levels of satisfaction, with 90% expressing pronounced contentment regarding the conference experience, compared to 85% in 2022. Moreover, nearly all respondents (98%) rated the relevance of conference content to Latino cancer science as excellent, with 93% regarding the conference as an exceptional platform for information exchange, compared to 79% in 2022. Impressions regarding session quality were overwhelmingly positive, with 90% of respondents indicating a high level of satisfaction, and all survey respondents acknowledging the objectivity, balance, and absence of commercial bias in the session content. Our results showed that the resounding positivity in attendee feedback reflects the conference's success in fostering meaningful engagement among researchers committed to alleviating Latino cancer health disparities. The ASCL conference facilitated an understanding of cultural nuances and barriers specific to the Latino community, stimulating collaborative efforts aimed at enhancing Latino health outcomes. Overall, this retrospective analysis affirms the conference's success in achieving its stipulated objectives and underscores the need of having consistently coordinated research endeavors to reduce Latino health disparities. Citation Format: Amelie G. Ramirez, Rebecca T. Jones, Matthew P. Banegas, Maria C Camargo, Gerardo Colon-Otero, Cliff Despres, Laura Fejerman, Filipa Lynce, Martin Mendoza, Patricia I. Moreno, Alejandro Recio-Boiles, Barbara Segarra-Vazquez, Sandi Stanford, Mariana Stern, Katherine Y. Tossas, Edward J. Trapido, Nicolette M Orozco. Advancing the science of cancer in Latinos conference [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B032.

Abstract Introduction Addressing cancer disparities by meeting people where they are is a crucial aspect of community-engaged research. The impact of this has been seen through the community outreach and engagement efforts of cancer centers across the country, with many focusing on churches, community events, and other trusted places. In the past four years, Mayo Clinic’s Cancer Health Equity Program (CHERP) has made a specific effort to decentralize clinical trials and community-engaged research by going to the places our community trusts and frequents. As a result, we partnered with a trusted leader in Jacksonville, Florida to engage with barbershops as sites for health information dissemination. We re-engaged a cohort of barbers who had previously worked with our outreach initiatives as part of the Community Engagement Alliance (CEAL) Against COVID-19 Disparities and recruited new ones for this phase of work. Methods Our community partner completed a training hosted by Florida A&M University on working with barbershops for community outreach and engagement research. The community partner then trained each barber on sharing health information, incorporating feedback from the previous cohort. Barbers were also trained to collect engagement and pre/post-test information to measure outcomes. Health information included COVID-19 prevention/ vaccine information and general cancer prevention information used in other community outreach and engagement initiatives. Results A total of 19 barbers engaged in this initiative; 9 were a part of our previous work with barbers and 10 were recruited for the new year of funding. The barbers all identified as Black and engaged with a total of 497 clients. Of the 497 clients, 91% identified as Black, and less than 5% identified as White, Asian, or Native American. 344 clients identified as male (69%), 147 as female (30%), 1 as transgender (0.2%), and 5 did not disclose their gender. The majority of participants were born between the 1960s and 2000s, with most reporting having a high school degree or GED (55%). Post-test information found evidence of knowledge change, including a 3.4% increase in those who responded understanding how COVID-19 is spread and a 4% increase in those who reported vaccines to be safe. Barbers also expressed their appreciation for being included in this initiative. Conclusion CHERP, in partnership with the community, is addressing disparities at different levels. One of the barriers the barbers had to overcome was hesitancy in sharing health-related topics. However, sustained initiatives, such as this one might overcome this barrier. This study’s engagement with barbershops to reach communities most impacted by cancer disparities points to the impact of barbershops as a site for cancer disparities research. Citation Format: Jessica Otero Machuca, Opeyemi Bolajoko, Jocelyn Turner, Folakemi Odedina. Decentralizing cancer disparities research: Barbershops as a foundation for community outreach and engagement [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B088.

Abstract Outcomes are poor in triple-class–exposed (TCE) relapsed and refractory multiple myeloma (R/RMM). In the phase 3 KarMMa-3 trial, patients with TCE R/RMM and 2 to 4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary end point; 13.3 vs 4.4 months; P < .0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median was 41.4 (95% CI, 30.9 to not reached [NR]) vs 37.9 (95% CI, 23.4 to NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI, 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE R/RMM. This trial was registered at www.ClinicalTrials.gov as #NCT03651128.

Background: The Clinical Treatment Score post-5 years (CTS5) is a risk stratification tool used to determine the risk of late recurrence in hormone receptor–positive (HR+), HER2-negative breast cancer (BC). Limited data exist on its use in HR+, HER2-positive (HER2+) BC. Patients and Methods: CTS5 was evaluated in HR+, HER2+ BC in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials. Results: A total of 1,862 patients with HR+, HER2+ BC without recurrence 5 years after enrollment were included. Overall, the CTS5 score was significantly associated with recurrence-free survival (RFS), with a hazard ratio (HR) of 1.35 (95% CI, 1.12–1.63; P=.002), but did not reach statistical significance in patients who received trastuzumab (n=829; HR, 1.29; 95% CI, 0.98–1.71; P=.07). CTS5 risk category was not significantly associated with RFS. In patients who received trastuzumab, other variables used in CTS5, including patient age and tumor size, were not significantly associated with RFS. N3 was significantly associated with worse outcomes (HR, 1.86; 95% CI, 1.09–3.17; P=.02) compared with N0–N1. Paradoxically, higher tumor grade was associated with better outcomes after 5 years in the multivariate analysis (HR, 0.71; 95% CI, 0.50–1.00; P=.05). The incidence of recurrences or deaths between years 5 to 10 was 10.6% in the CTS5 low-risk category, 5.6% in the intermediate-risk category, and 9.8% in the high-risk category. Conclusions: The CTS5 model does not accurately predict the risk of late recurrence in HR+, HER2+ BC treated with adjuvant trastuzumab in the N9831 and B-31 trials. This study underlines the need to develop a new prognostic model to better delineate the risk of late recurrence in patients with HR+, HER2+ BC receiving adjuvant trastuzumab. ClinicalTrials.gov identifiers: NCT00005970 (NCCTG N9831) and NCT00004067 (NRG/NSABP B-31).

Background Postoperative urinary retention (POUR) is a common and distressing surgical complication that may be associated with the pharmacological reversal technique of neuromuscular blockade (NMB). Objective This study aimed to investigate the impact that POUR has on medical charges. Methods This was a retrospective observational study of adult patients undergoing select surgeries who were administered neuromuscular blockade agent (NMBA), which was pharmacologically reversed between February 2017 and November 2021 using data from the PINC-AI™ Healthcare Database. Patients were divided into 2 groups: those experiencing POUR (composite of retention of urine, insertion of temporary indwelling bladder catheter, insertion of non-indwelling bladder catheter) during index hospitalization following surgery and those without POUR. Surgeries in inpatient and outpatient settings were analyzed separately. A cross-sectional comparison was performed to report total hospital charges for the 2 groups. Furthermore, patients experiencing subsequent POUR events within three days after discharge from index hospitalization were studied. Results A total of 330 838 inpatients and 437 063 outpatients were included. POUR developed in 13 020 inpatients and 2756 outpatients. Unadjusted results showed that POUR was associated with greater charges in both inpatient ($92 529 with POUR vs $78 556 without POUR, p < .001) and outpatient ($48 996 with POUR vs $35 433 without POUR, p < .001) settings. After adjusting for confounders, POUR was found to be associated with greater charges with an overall mean adjusted difference of $10 668 (95% confidence interval [CI] $95 760-$11 760, p < .001) in inpatient and $13 160 (95% CI $11 750-$14 571, p < .001) in outpatient settings. Charges associated with subsequent POUR events following discharge ranged from $9418 inpatient charges to $1694 outpatient charges. Conclusions Surgical patients who were pharmacologically reversed for NMB and developed a POUR event incurred greater charges than patients without POUR. These findings support the use of NMB reversal agents associated with a lower incidence of POUR.

TPS3173 Background: ELU001, pasifolate exatecan, is an ultra-small nanoparticle drug conjugate, known as a CDC (~6 nm), designed to target and penetrate into solid tumors. Due to its size, ELU001 exhibits rapid renal elimination which is expected to reduce or eliminate the toxicities associated with many antibody drug conjugates. ELU001 has ~13 folic acid targeting moieties and ~21 cathepsin-B cleavable exatecan topoisomerase-1 inhibitor payloads covalently bound to short polyethylene glycol chains surrounding a silica core, the C’Dot. ELU001 binds to cancer cells expressing FRα and is internalized into the lysosome where it releases the exatecan payload. ELU001’s dose escalation study reported at ESMO Congress 2023 (1), examined weekly, bi-weekly (Q2W), and tri-weekly schedules over a range of doses in 42 patients. The study revealed that ELU001 could be administered safely and identified a dose level and schedule for the Expansion Studies described below. 22 of the patients with ovarian or endometrial cancers had >1 post-baseline scan(s), of these 2 had a PR and 19 had SD by RECIST v1.1 criteria. ELU001 demonstrated activity against tumors across a range of FRα expression levels, from low to high, retrospectively assessed using the VENTANA FOLR1 RxDx assay and the PS2+ scoring system. Methods: The current multicenter, Tumor Group Expansion open-label phase 1/2 clinical trial investigates ELU001 in patients with ovarian and endometrial cancers and is enrolling three cohorts; 1) ovarian cancer with high FRα expression, 2) ovarian cancer with moderate and low expression and 3) endometrial cancer with low to high expression with assessments based upon the PS2+ scoring system (high = ≥ 75%, moderate = ≥ 50% to < 75%, low = 25% to < 50%, negative = <25% of tumor cells with 2+ or 3+ staining intensity). An initial exploratory dose of 2.0 mg/m2 Q2W was employed in all three cohorts and a second dose of 1.7 mg/m2 Q2W will be studied in the ovarian cancer cohorts. Patients will ultimately be randomized to one of two or more doses to optimize dosing for registration. Primary endpoint: Objective Response Rate (ORR); secondary endpoints include DOR, PFS, TFST, PFS2, OS, adverse events, PK, and ADA assessments. Approximately 20 patients per tumor group will be recruited in the U.S. 1. Ann. Oncol. (2023) 34 (suppl_2): S458-S497. Clinical trial information: NCT05001282 .

Abstract Background: Tertiary lymphoid structure (TLS) is an organized form of ectopic lymphoid aggregates (LA) with secondary lymphoid organ structure. Several studies showed that the presence of TLS associates with improved outcomes in multiple cancers when treated with immune checkpoint inhibitors. However, data is currently limited regarding TLS and outcomes in HER2+ breast cancer patients (pts) treated with adjuvant trastuzumab. Furthermore, distinguishing TLS and simple LA is challenging in standard hematoxylin and eosin (H&E) staining, particularly when the germinal center is absent. Emerging studies also showed the prognostic value of MHC expression in breast cancer but mainly in triple-negative breast cancer. In this study, we evaluated integrated pathological quantification and genomic data to assess functional TLS in association with MHC expression and outcomes in the N9831 trial. Methods: Pathological evaluation of LA in H&E slides from pts treated in Arm A (chemotherapy alone) and Arm C (chemotherapy with concurrent trastuzumab) in N9831 was performed. NanoString was used to quantify mRNA of MHC class I and II expression as well as TLS-related immune genes, including IFNG, ICOSLG, CXCL13, CXCR3, BCL6, IL21R, ICOS, PDCD1, CXCR5, CXCL9, TBX21, CD38, CXCL10, CLXCL11, IL21, CD200, CD19, MS4S1. Wilcoxon rank sum test, Chi-squared test, Kaplan-Meier method, and Cox regression model were used to evaluate the association between LA and baseline characteristics, MHC expression, and outcomes. Results: LA was evaluated in 526 pts in Arm A and 485 in Arm C. Greater number of LA was significantly associated with stromal tumor-infiltrating lymphocytes (sTILs), hormone receptor negative, and higher tumor grade, but not stage and age. Using multivariable Cox regression analysis, increasing numbers of LA were associated with improved recurrence-free survival in both arms combined (RFS, p 0.028). However, when evaluating each arm separately, LA was associated with improved RFS only in Arm A (HR 0.6, 95%CI 0.43-0.84, p 0.003) but not in Arm C (HR 0.72, 95%CI 0.47-1.1, p 0.134). We further evaluated TLS-related immune genes in 252 pts in Arm C with LA ≥ 1. As a continuous variable, higher expression of BCL6 (HR 0.61, 95%CI 0.41-0.92, p 0.019) and IL21R (HR 0.78, 95%CI 0.62-0.98, p 0.03) were associated with improved RFS in Arm C pts with LA ≥ 1. However, these genes were not significantly associated with outcomes in Arm C pts without LA with BCL6 (HR1.07, 95%CI 0.67-1.71, p 0.776) and IL21R (HR 0.96, 95%CI 0.71-1.29, p 0.775). Moreover, we evaluated differential gene expression between tumors with LA ≥ 1 with high BCL6 vs. LA 0. All MHC class I and II (HLA A, B, C, E, DQ, DM, DO, DP, and DQ) were significantly higher in tumors with LA ≥ 1 with high BCL6 (p &lt; 0.001). Conclusion: A greater number of LA was associated with improved outcomes in pts with early-stage HER2+ breast cancer, particularly when treated with chemotherapy alone. Using histologic and genomic integration with the combination of pathological LA and TLS-related immune genes, we identified that pts with functional TLS with LA ≥ 1 and higher expression of BCL6 or IL21R had significantly improved outcomes when treated with trastuzumab. High MHC class I and II expressions are associated with the presence of functional TLS, underscoring the crucial role of antigen presentation in the generation of an effective adaptive immune response. Support: U10 CA180821, U10 CA180882, U24 CA196171, https://acknowledgments.alliancefound.org; Genentech; Clinicaltrials.gov Id: NCT00005970 Citation Format: Saranya Chumsri, Tracy Shachner, Zhuo Li, Nadine Norton, Alvaro Moreno-Aspitia, Gerardo Colon-Otero, Edith Perez, Aziza Nassar, E. Thompson, Keith Knutson. MHC Class I and II Expression, Functional Tertiary Lymphoid Structure (TLS), and Outcomes in Early-Stage HER2-Positive (HER2+) Breast Cancer in NCCTG N9831 (Alliance) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-04.