Winship Cancer Institute Research Articles

Real-World Outcomes in Patients with Advanced Penile Squamous Cell Carcinoma Receiving Immune Checkpoint Inhibitors: A Single Institution Experience

ABSTRACT Introduction Advanced penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with a poor prognosis and an unmet need for biomarkers. We performed a retrospective evaluation of real-world efficacy, safety outcomes, and baseline inflammatory biomarkers in patients with advanced pSCC treated with immune checkpoint inhibitors (ICIs). Methods We performed a retrospective review of patients with advanced pSCC who received ICIs from 2012 to 2023 at the Winship Cancer Institute of Emory University in Atlanta, GA. Demographics, disease characteristics, and optimal cutoffs of baseline biomarkers obtained before ICI initiation were described. Human papillomavirus (HPV)/p16+ status was determined by immunohistochemistry. Programmed death-ligand 1 (PD-L1) positivity was defined as >1%. Immune-related adverse events (irAEs) were graded per Common Terminology Criteria for Adverse Events criteria and captured through clinical documentation. Clinical benefit was defined as complete response, partial response, or stable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and univariate Cox regression (UVA) using a significance level set at p < 0.05. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were collected from complete blood count data. Results Twenty-one patients were included of whom 71.4% were White and 28.6% were Black. Median age at ICI initiation was 56 years (38–76 years). Most patients had Eastern Cooperative Oncology Group performance status ≥2 (61.9%). At diagnosis, 4.8%, 33.3%, and 61.9% were stage 2, 3, and 4, respectively, of whom eight patients had initial distal metastases. Of patients with available data, 7 of 11 patients (63.6%) were PD-L1+ and 8 of 9 (89%) patients were HPV+. Median follow-up was 8.4 months and median time to ICI treatment from diagnosis was 15.6 months. ICI was first line (1L) in 1 patient (4.8%), 2L in 13 (61.9%), 3L in 6 (28.6%), and 4L in 1 (4.8%). Five patients achieved clinical benefit of whom three had partial response and two had stable disease. Median OS was 8.2 months (95% CI, 2.3–15.7) and PFS was 1.9 months (95% CI, 1.3–3.2). Notably, three patients with PD-L1 positivity, microsatellite instability (MSI)-high, or high tumor mutational burden (TMB) demonstrated response to ICI. Higher baseline NLR (hazard ratio, 10.0; 95% CI, 2.73–54.2) at optimal cutoff was associated with shorter OS and PFS on UVA. Three patients (14.3%) developed grade 3/4 ICI-related adverse events. Conclusions Our real-world analysis summarizes our institutional experience and provides granular clinical and molecular attributes of patients with therapeutic response, which may aid in patient stratification within ICI-based clinical trials. Overall, we confirm poor response rates of pSCC to ICI in an unselected approach, consistent with multicenter studies. ICIs may be effective and tolerable therapy in a subset of patients. NLR may be a potential biomarker to assess ICI response in pSCC.

Essential Components of an Electronic Patient-Reported Symptom Monitoring and Management System

Multicomponent electronic patient-reported outcome cancer symptom management systems reduce symptom burden. Whether all components contribute to symptom reduction is unknown. To deconstruct intervention components of the Symptom Care at Home (SCH) system, a digital symptom monitoring and management intervention that has demonstrated efficacy, to determine which component or combination of components results in the lowest symptom burden. This randomized clinical trial included participants who were older than 18 years, had been diagnosed with cancer, had a life expectancy of 3 months or greater, were beginning a chemotherapy course planned for at least 3 cycles, spoke English, and had daily access and ability to use a telephone. Eligible participants were identified from the Huntsman Cancer Institute, University of Utah (Salt Lake City), and from Emory University Winship Cancer Institute, including Grady Memorial Hospital (Atlanta, Georgia), from August 7, 2017, to January 17, 2020. Patients receiving concurrent radiation therapy were excluded. Dates of analysis were from February 1, 2020, to December 22, 2023. Participants reported symptoms daily during a course of chemotherapy and received automated self-management coaching with an activity tracker without (group 1) and with (group 2) visualization, nurse practitioner (NP) follow-up for moderate-to-severe symptoms without (group 3) and with (group 4) decision support, or the complete SCH intervention (group 5). The primary outcome, symptom burden, was assessed as the summed severity of 11 chemotherapy-related symptoms rated on a scale of 1 to 10 (with higher scores indicating greater severity), if present. The 757 participants (mean [SD] age, 59.2 [12.9] years) from 2 cancer centers were primarily female (61.2%). The most common cancer diagnoses were breast (132 [17.4%]), lung (107 [14.1%]), and colorectal (99 [13.1%]) cancers; 369 patients (48.7%) had metastatic disease. The complete SCH intervention including automated self-management coaching and NP follow-up with decision support (group 5) was superior in reducing symptom burden to either of the self-management coaching groups, as shown by the mean group differences in area under the curve (group 1, 1.86 [95% CI, 1.30-2.41] and group 2, 2.38 [95% CI, 1.84-2.92]; both P < .001), and to either of the NP follow-up groups (group 3, 0.57 [95% CI, 0.03-1.11]; P =.04; and group 4, 0.66 [95% CI, 0.14-1.19]; P = .014). Additionally, NP follow-up was superior to self-management coaching (group 1 vs group 3, 1.29 [95% CI, 0.72-1.86]; group 1 vs group 4, 1.20 [95% 12 CI, 0.64-1.76]; group 2 vs group 3, 1.81 [95% CI, 1.25-2.37]; and group 2 vs group 4, 1.72 [95% CI, 1.17-2.26]; all P < .001), but there was no difference between the 2 self-management coaching groups (-0.52 [95% CI, -1.09 to 0.05]; P = .07) or between the 2 NP groups (-0.10 [95% CI, -0.65 to 0.46]; P = .74). In this randomized clinical trial of adult participants undergoing chemotherapy treatment for cancer, the complete intervention, rather than any individual component of the SCH system, achieved the greatest symptom burden reduction. These findings suggest that a multicomponent digital approach to cancer symptom management may offer optimal symptom burden reduction. ClinicalTrials.gov Identifier: NCT02779725.

PD-L1 and nectin-4 expression and genomic characterization of bladder cancer with divergent differentiation.

Bladder cancer with divergent differentiation (BCDD) comprises a heterogenous group of tumors with a poor prognosis, and differential expression of nectin-4 and programmed death ligand-1 (PD-L1) has been reported in BCDD. Importantly, nectin-4 expression in bladder cancer is associated with response to enfortumab vedotin, and PD-L1 expression is associated with responses to immune checkpoint inhibitors (ICIs). The authors conducted a retrospective review identifying 117 patients with advanced or metastatic BCDD who were treated at Winship Cancer Institute from 2011 to 2021. They performed immunohistochemistry staining for nectin-4 and PD-L1 expression by histologic subtype as well as genomic analysis of these patients, including RNA sequencing, whole-exome sequencing, and fusion detection analysis as well as a subgroup genomic analysis of patients with BCDD who received ICIs. The results indicated that nectin-4 expression was highest in the groups who had the squamous and plasmacytoid subtypes, whereas the group that had the sarcomatoid subtype (70.8%) had the highest proportion of PD-L1-positive patients. Genomic analysis yielded several key findings, including a 50% RB1 mutation rate in patients who had small cell BCDD, targetable PIK3CA mutations across multiple subtypes of BCDD, and significantly higher expression of TEC in responders to ICIs. In this study, the authors identified clinically relevant data on nectin-4 and PD-L1 expression in patients with rare bladder tumors. They also identified several novel findings in the genomic analysis that highlight the role of precision medicine in this population of patients. Larger, prospective studies are needed to validate these hypothesis-generating data.

Analysis of travel burden and travel support among patients treated at a comprehensive cancer center in the Southeastern United States.

Travel burden leads to worse cancer outcomes. Understanding travel burden and the level and types of travel support provided at large cancer centers is critical for developing systematic programs to alleviate travel burden. This study analyzed patients who received travel assistance, including their travel burden, types and amount of travel support received, and factors that influenced these outcomes. We analyzed 1063 patients who received travel support from 1/1/2021 to 5/1/2023 at Winship Cancer Institute, in which ~18,000 patients received cancer care annually. Travel burden was measured using distance and time to Winship sites from patients' residential address. Travel support was evaluated using the monetary value of total travel support and type of support received. Patients' sociodemographic and clinical factors were extracted from electronic medical records. Area-level socioeconomic disadvantage was coded by the Area Deprivation Index using patient ZIP codes. On average, patients traveled 57.2 miles and 67.3min for care and received $74.1 in total for travel support. Most patients (88.3%) received travel-related funds (e.g., gas cards), 5% received direct rides (e.g., Uber), 3.8% received vouchers for taxi or public transportation, and 3% received combined travel support. Male and White had longer travel distance and higher travel time than female and other races, respectively. Patients residing in more disadvantaged neighborhoods had an increased travel distance and travel time. Other races and Hispanics received more travel support ($) than Black and White patients or non-Hispanics. Patients with higher travel distance and travel time were more like to receive travel-related financial support. Among patients who received travel support, those from socioeconomically disadvantaged neighborhoods had greater travel burden. Patients with greater travel burden were more likely to receive travel funds versus other types of support. Further understanding of the impact of travel burden and travel support on cancer outcomes is needed.

Precision medicine preceptorship in breast and lung cancer for Latin American oncologists.

9040 Background: Cancer is the second leading cause of death in Latin America. Integrating genomic discoveries into patient care could improve morbidity and mortality; however economic barriers to capacity development and access to therapeutics remain. In response to an RFP for a preceptorship for oncologists from Latin America, Emory’s Winship Cancer Institute (WCI) developed a 2-week immersion involving didactics, clinical exposures, and research meetings to increase knowledge and competence of breast and lung cancer genomics. Methods: Interviews with Latin American medical oncologists, Latin America Lung Cancer Association (LALCA) leadership, and literature review were conducted to understand areas of unmet need in oncology training. A gap in knowledge and practice of genomic management of breast and lung cancer was identified and informed development of didactic and clinical exposures. The WCI website, International Association for the Study of Lung Cancer (IASLC) and LALCA publicized the program. Medical oncologists within 6 years of final oncology training applied. Participants completed a baseline needs assessment, pre-program survey to assess goals and confidence in skills, and post-program interview to evaluate the program and reassess confidence in skills. Instruments were developed with WCI’s Intervention, Development, Dissemination and Implementation Shared Resource. WCI faculty were interviewed for feedback. Results: WCI hosted 12 Latin American oncologists over 3 two-week preceptorships between 2020-23, coinciding with local scientific meetings. All participants reported the program was a valuable use of time, valuable for career development and rated the program as excellent/very good. 92% reported the program met their goals and felt engaged all/most of the time. 75% rated attendance at breast and lung cancer clinics, didactics, research meetings, tumor boards as very/extremely valuable. Two-thirds intended to make changes (apply knowledge, improve communication, work with other providers like nurses, aid students in research, improve flow of activity when seeing patients, incorporate clinical research into daily practice, and add immunotherapy) in their practice at home institutions. Phase 1 and surgical oncology clinics were deemed least helpful. Themes emerged from faculty interviews: be strategic about the number of learners in clinic, characterize learner preferences and prior training/experience, articulate the preceptorship’s long-term goals, and include time to team-build. Conclusions: Participants gained exposure to the latest molecular diagnostics and systemic treatments, appreciation for optimal team-based cancer care, and how clinical research drives development of novel biomarkers and therapeutics. Future goals include expanding program access to oncologists from other low- and middle-income countries and promoting post-program collaborations.

Clinical outcomes in patients with early-stage breast cancer in a racially and ethnically diverse patient population.

e12532 Background: Despite the growing evidence that substantial disparities exist in breast cancer care per socioeconomic status, the racial and ethnic disparities that contribute to clinical outcomes in patients with early breast cancer are not well understood. This analysis attempts to better characterize these differences in a diverse group of patients with early breast cancer. Methods: Patients were identified from an institutional database from the Winship Cancer Institute, which included those with pathologic stage I-III breast cancer with varying hormone receptors (HR) and HER2 receptor status who received care between 1999-2023. Patients with ductal carcinoma in-situ (DCIS) and with metastatic breast cancer at diagnosis were excluded from this retrospective analysis. Using variables such as race, treatment received, pathological stage, tumor grade, and histology, we performed univariate and multivariate analysis for IDFS, defined as pts who are alive and free of any breast or other cancer. Results: 449 patients were included, which comprised of 148 non-Hispanic African American (33%) and 301 (66%) Caucasian women. Mean age at diagnosis was 60; 77.3% of patients were post-menopausal, and 79.1% received operable endocrine therapy. 76.4% of patients had invasive ductal carcinoma (IDC) and 13.1% invasive lobular carcinoma (ILC). Only 9.8% received chemotherapy. In univariate analysis, patients who were triple negative (n=30, 6.8%) had worse IDFS compared to those who were HR+/HER2- (n=351) (Hazard Ratio=2.49, p=0.036) Additional patients with larger tumors with pT2-pT4 (n=133, 30.4%) had worse IDFS compared to those with pT0-pT1 (p=297, 67.8%) tumors (HR=2.04, p=0.014). There were no significant differences in clinical outcomes by patient race or by lymph node involvement. Conclusions: In our lower-risk, racially diverse cohort, our findings demonstrate that patients with HR-/HER2- breast cancer and larger tumors have worse IDFS. More analyses should be performed on a population with higher-risk patients and larger cohort. Future studies should continue to focus on early screening, as well as novel therapeutics to treat HR-/HER2- disease.

Racial differences in therapies received by patients with cutaneous T cell lymphoma (CTCL): A single center retrospective cohort analysis.

e23141 Background: Black patients with cutaneous T-cell lymphoma (CTCL) have increased risk of mortality and higher rates of treatment complications compared to other racial groups, however, drivers of these disparities are poorly understood. Recent advances in novel targeted therapies, such as mogamulizumab and brentuximab vedotin (BV), have demonstrated improved survival compared to standard therapies. We aimed to identify treatment patterns and clinical outcomes in patients with mycosis fungoides and Sezary syndrome (MF/SS) to better understand potential drivers underlying these racial disparities. Methods: We performed a retrospective review of 282 patients with a histopathologic diagnosis of advanced stage MF/SS seen at the Winship Cancer Institute of Emory University from 2000-2023. Clinical data was collected from the electronic medical record and included demographics, histopathologic findings, therapies received, highest disease stage reached, and survival. Differences in baseline characteristics and treatments were assessed using univariate analysis. The association between race, insurance status, disease stage, and category of treatment was assessed using multivariable analysis of overall survival (OS). Results: The cohort was comprised of an even distribution of patients identifying as Black (50%) and white (47.5%). Median age at diagnosis was 61 years (range, 12-91), and Black patients had an earlier age of diagnosis compared to white (median 52 vs. 65.5 years, p &lt; 0.001). The majority of patients had a pathological diagnosis of MF (79.1%). Large cell transformation was seen in 24.8%. Most common stage was stage 2b (36.2%); other stages included 3a (18.1%), 3b (4.3%), 4a1 (19.1%), 4a2 (13.1%), and 4b (9.2%). Systemic therapies were divided into three groups: standard chemotherapy, biologics (interferon, retinoids, extracorporeal photopheresis, and methotrexate), and novel agents (mogamulizumab, BV, and clinical trials). Median OS was 47.5 months (range, 2-246 months), and was greater in patients who received treatment with novel agents (hazard ratio 0.46, 95%, CI 0.29-0.73, p &lt; 0.001). Black patients were less likely to receive photopheresis and local radiation compared to white patients (36.73% vs. 63.27% and 39.53% vs. 60.47%, p &lt; 0.05, respectively), however, there were no differences in the receipt of novel agents by race. There were no differences in OS between Black and white patients. Conclusions: While we did find some differences in treatment patterns by race, these did not translate to a difference in outcomes. Importantly, in this cohort of patients who received similar rates of novel targeted therapies across racial groups, there were no differences in survival by race. These findings suggest that factors such as access to novel targeted therapies may play a role in the well-documented racial disparities in treatment outcomes.

Enfortumab vedotin plus pembrolizumab in the treatment of locally advanced or metastatic bladder cancer of variant histology: A phase II study.

TPS4615 Background: Bladder cancers of variant histology (BCVH) account for up to 25% of bladder cancer incidence and affected patients (pts) usually have poor outcomes. The treatment options are limited due to the underrepresentation or exclusion of BCVH pts from trials for locally advanced or metastatic urothelial cancer (mUC). Enfortumab vedotin (EV) is an antibody-drug conjugate specific for Nectin-4. In the EV 302 Phase III trial, EV+pembrolizumab (pembro) significantly prolonged overall survival (OS) compared to platinum-based chemotherapy in mUC (HR 0.47, 95% CI 0.38-0.58) and was recently FDA-approved as standard of care in 1L mUC. Translational studies from our center show Nectin-4 expression in many BCVH pts and data support immune-checkpoint inhibitor (ICI) activity in subsets of these pts. We hypothesize the presence of clinical activity of this combination in BCVH. Therefore, we designed this trial to assess the efficacy and safety of EV+pembro in locally advanced or metastatic BCVH (mBCVH). Methods: This is a Phase II, open-label, single-center trial at the Winship Cancer Institute of Emory University (NCT05756569) for pts with mBCVH. Pts will receive pembro 200mg IV on Day 1 and EV 1.25mg/Kg IV on Days 1 and 8 of a 21-day cycle for up to two years. The eligibility criteria include histologically confirmed variant histology or non-urothelial bladder cancer of epithelial origin including squamous cell carcinoma and adenocarcinoma (according to the WHO 2016 Classification), ECOG 0-1, and any line of therapy. Pts with neuroendocrine bladder cancer, non-epithelial cancers (e.g. sarcoma, lymphoma), prior ICI and/or EV treatment are excluded. Overall response rate (ORR) per RECIST 1.1 is the primary outcome and will be tested using Simon's two-stage design (n=25). The first interim analysis is planned after 15 patients. The desirable target is ORR≥30% relative to a null hypothesis of ORR ≤10%. This statistical design yields a type I error rate of 0.05 and a power of 80% for a true ORR≥30%. Key secondary outcomes include OS, progression-free survival, duration of response, and incidence of adverse events per CTCAE v5.0. Correlative biomarker analyses using blood- and tissue-based assays will be conducted during screening and at disease progression. The trial is currently open for enrollment. Clinical trial information: NCT05756569 .

Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA

Currently, the use of radiotherapy alone for people with multiple myeloma is limited to palliation of pain, pending fracture, and control of spinal-cord compression. Single immune-checkpoint inhibitors, such as anti-programmed death-1 (anti-PD1), have not been successful. We aimed to evaluate the activity and safety of the combination of pembrolizumab and low-dose, single-fraction, hypofractionated radiotherapy to treat patients with relapsed or refractory multiple myeloma. For this prospective, single-centre, single-group, open-label, phase 2 trial, we recruited patients with relapsed or refractory multiple myeloma from the Winship Cancer Institute (Emory University, Atlanta, GA, USA). Key inclusion criteria were aged 18 years or older, Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, relapsed or refractory multiple myeloma as indicated by progression under International Myeloma Working Group (IMWG) criteria, and adequate candidacy for both pembrolizumab and radiotherapy. Baseline and post-treatment assessments were serial bone-marrow biopsy, peripheral blood collections, staging, serial serum and urine paraprotein analysis, serial PET-CT imaging, and a physical examination. On day 1, patients received hypofractionated 8 gray in 1 fraction (8 Gy/1 fx) radiotherapy to either symptomatic or progressing extra-osseous or osseous myeloma sites. Patients also received pembrolizumab (200 mg/kg intravenously) on day 2 or 3, then once every 3 weeks (±7 days) for 2 years or until progressive disease, unacceptable toxicity, withdrawal of consent, loss to follow-up, or death. Dose reduction and interruptions were not allowed. The primary outcome was acute toxicity defined as grade 3 or worse toxicity at 3 months within the radiated site when used in combination with pembrolizumab. All patients were analysed per protocol and included in safety analyses. This trial is registered on ClinicalTrials.gov (NCT03267888); it is completed and closed to accrual. 32 patients were screened between June 1, 2018, and Sept 2, 2022, and 25 were enrolled in the trial and treated on protocol. Of the 25 treated patients, 11 (44%) were female and 14 (56%) were male. 19 (76%) patients were White and six (24%) were Black or African American. Toxicity, as the primary outcome, was deemed to be acceptable as no grade 4 or 5 adverse events were observed. At 3-month follow-up, eight (32%) of 25 patients had treatment benefit (one had stable disease, three had partial response, two had very good partial response, and two had complete response). There was no grade 3 or worse radiation-related toxicity within irradiated volumes. One (4%) patient of the 25 who received combination treatment had a grade 3 pembrolizumab-related adverse event. There were no treatment-related deaths. Combination treatment of low-dose, single-fraction radiotherapy with pembrolizumab was safe, with early promise of response activity. Our approach could be an option for patients with relapsed or refractory multiple myeloma who have not responded to previous treatment. Larger trials to substantiate our findings are needed. Merck Sharp & Dohme.

Abstract PO3-16-09: Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center

Abstract Background: Trastuzumab Deruxtecan (T-DXd) is an antibody-drug conjugate originally approved for use in patients with HER2–positive metastatic breast cancer (MBC). In June 2022, data from the DESTINY-Breast04 trial revealed a near-doubling of progression-free survival (PFS) and significantly improved overall survival (OS) for patients with HER2-low MBC (immunohistochemistry [IHC] grade 1+ or IHC2+ in situ hybridization [ISH]-negative) treated with T-DXd versus standard-of-care chemotherapy. The data from this clinical trial led to the approval of T-DXd for use in patients with HER2-low MBC. However, the DESTINY-Breast studies completed to date have included &amp;lt; 5% black patients. This retrospective study of patients at a racially diverse NCI Comprehensive Cancer Center was designed to study whether T-DXd in a real-world population are comparable to published data. Methods: A retrospective chart review was conducted and identified 72 patients with HER2-low and HER2-positive MBC who received T-DXd between December 2019 and March 2023 at the Winship Cancer Institute at Emory University. Data collected for all patients included demographics, prior breast cancer history, T-DXd -specific and post-T-DXd treatment, and clinical outcomes where applicable. Results: Of the 103 patients who were dosed with T-DXd, 55 (53.4%) had HER2-positive disease, and 48 (46.7%) patients had HER2-low disease. 71 (68.9%) patients had hormone-receptor positive disease and 32 (31.1%) patients had hormone-receptor negative disease. The overall study population was 46% Caucasian; 38% African American; 13% Asian; 4% Unreported. The average number of cycles received was 11 (on treatment an average of 8 months). Pneumonitis occurred in 5 patients (4.9%). HER2-positive patients were typically on T-Dxd for a greater number of cycles than HER2-low patients (Table 1). Additionally, patients with brain metastases were, on average, treated with T-Dxd longer than patients without brain metastases, 14.5 versus 9 cycles. The number of cycles of T-Dxd received, the need for dose reduction, and incidence pneumonitis did not differ significantly between black and white patients. The data for this study is preliminary 48% of the patient population are still actively undergoing T-Dxd treatment. Conclusion: This study reviewed and analyzed T-Dxd treatment in a diverse population of both HER2-positive and HER2-low MBC patients, and in this study, outcomes of treatment did not differ by race. More attention to this topic is needed in future studies of larger populations, along with increased efforts to enroll diverse patient populations in clinical trials. Table 1. Citation Format: Jane Meisel, Maisey Ratcliffe. Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center [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 PO3-16-09.

Abstract PO5-10-06: A Pilot Study for Clinical Research Nurse Navigation at an Urban NCI-Designated Comprehensive Cancer Center

Abstract Background: Breast cancer is now the leading cause of cancer death for non-Hispanic Black women in Georgia with non-Hispanic Black women 40% more likely to die of breast cancer compared to White women. Inadequate representation of patients in clinical trials may contribute to health care inequity, though prior work has also shown disparate outcomes on similar clinical trials at Emory, suggesting differences in tumor biology may also be contributing to the disparity. Improving diversity in trial participation is imperative to better understand these differences, particularly with newer molecularly targeted therapies. We aimed to utilize Clinical Trials Nurse Navigation to increase clinical trial enrollment at an urban NCI-designated comprehensive care center in Atlanta, Georgia. Methods: A prospective pilot study was conducted investigating the role of a Clinical Research Nurse as a dedicated Clinical Trials Nurse Navigator to identify, pre-screen, and refer potential patients to both breast and next generation sequencing (NGS)-driven basket clinical trials at the Winship Cancer Institute at Emory University. The role also included centralizing all molecular data from patients with stage IV breast cancer into a database as a tool to refer patients to NGS-driven clinical trials. This role expands upon the Institute’s current research nursing scope to better meet the needs of our diverse patient population. Our catchment area is 35% non-Hispanic Black or African American. The nurse prescreened patients with stage IV breast cancer from breast oncology clinic templates and the breast NGS database to match them with clinical trials, with a particular emphasis on patients with stage IV triple negative breast cancer. The study began in January 2022 and is currently ongoing. Results: Since study initiation in January 2022, there has been a 27% increase in breast cancer clinical trial enrollment over a 12-month period. Over the last 6 months from January 2023, this has increased even further with 57 patients enrolled onto breast cancer clinical trials compared to a total enrollment of 70 patients onto breast cancer clinical trials in 2022 (Table 1). Of these patients, 11% enrolled in NGS-driven clinical trials in 2022 to present compared to 0% in 2021. Twenty-two (31.4%) non-Hispanic Black women enrolled onto breast cancer clinical trials in 2022 with another 21 (36.8%) non-Hispanic Black women enrolled thus far in 2023 (Table 1). Conclusion: Disparities in clinical trial enrollment may contribute to racial inequities in breast cancer outcomes. Implementation of clinical research nurse navigation has successfully improved clinical trial enrollment and diversity in clinical trial enrollment at our urban cancer center. Through increasing clinical trial prescreening, centralizing an NGS database, and dedicated nurse support to allow patients to navigate onto clinical trials, we achieved a 21% improvement in clinical trial enrollment from 2021 to 2022 and are on track to increase enrollment by 200% by the end of 2023. Clinical trials nurse navigators serve as an essential link between clinical trial patients and their providers, and should strongly be considered a key component of all clinical trials programs. Table 1 Breast Working Group Patient Enrollment by Race and Ethnicity, 2019-2023 Citation Format: Lizzie Huckaby, Maisey Ratcliffe, Madison Canning, Demetria Smith-Graziani, Kevin Kalinsky, Manali Bhave. A Pilot Study for Clinical Research Nurse Navigation at an Urban NCI-Designated Comprehensive Cancer Center [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 PO5-10-06.

Abstract 879: The AVERON Notebook to discover druggable cancer dependencies through the mutant-directed protein-protein interactions

Abstract Cancer is a devastating disease that takes more than 10 million lives every year. The genomic alterations, such as mutations in cancer driver genes, can disrupt the essential networks of protein-protein interactions (PPIs), dysregulating major oncogenic pathways and inducing the transformation. While some mutations can disrupt existing PPIs, others can create neomorph PPIs (neoPPIs), which are unnatural for wild-type counterparts. Discovery of such mutant-created neoPPIs is vital for understanding the molecular mechanisms of mutant-driven tumorigenesis and developing new personalized clinical strategies in cancer. However, systematic experimental interrogation of the clinical significance and biological functions of neoPPIs is highly challenging. To address this critical challenge, we develop a novel computational platform called AVERON Notebook for identifying new Actionable Vulnerabilities Enabled by Rewired Oncogenic Networks. The AVERON employs specially designed algorithms and statistical techniques to i) Assess and compare the levels of neoPPIs in cancer patients; ii) Examine their impact on clinical outcomes; iii) Identify distinctive sets of signature genes and oncogenic pathways regulated by individual neomorph PPIs; and iv) Discover clinically significant neoPPI-regulated genes with available clinical compounds and approved drugs. Together, the AVERON Notebook provides a powerful tool for exploring the functional consequences of tumor-driving mutations mediated through the neoPPI networks and sheds new light on previously unexplored clinically actionable dependencies enabled by neomorph PPIs in cancer patients. The AVERON Notebook is freely available onGitHub: https://github.com/aivanovlab/averon_notebook and Code Ocean: https://doi.org/10.24433/CO.7986101.v1 Acknowledgments: This work was supported in part by NCI’s Informatics Technology for Cancer Research (ITCR) Program (R21CA274620, A.A.I.), Mary Kay Foundation Grant for Cancer Research (A.A.I), NCI Emory Lung Cancer SPORE (P50CA217691, H.F.), NCI P01CA257906 (H.F.), Career Enhancement Program (A.A.I., P50CA217691), Winship Cancer Institute (NIH 5P30CA138292). Citation Format: Hongyue (Nicole) Chen, Sean Yeung, Brian Revennaugh, Haian Fu, Andrey A. Ivanov. The AVERON Notebook to discover druggable cancer dependencies through the mutant-directed protein-protein interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 879.

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ON THE BACK COVER: CLIK‐1 (shown in green) is a calponin‐related actin‐binding protein that is predominantly expressed in the body wall muscle of the nematode Caenorhabditis elegans. Overlaps between CLIK‐1 and actin filaments (shown in magenta) generate the whitish green appearance of the sarcomeres.Credit: Shoichiro Ono, Winship Cancer Institute, Emory University School of Medicine image

A Randomized Phase II Study of Daratumumab, Ixazomib, and Dexamethasone (DId, Arm A) Vs Daratumumab, Bortezomib and Dexamethasone (DVd) Followed By Daratumumab, Did (Arm B) in Newly Diagnosed Multiple Myeloma (DeRIVE) Study

Introduction: The safety and efficacy established by daratumumab (a CD38 monoclonal antibody)-based induction therapies for both transplant-eligible myeloma patients (based on CASSIOPEIA, and GRIFFIN trials) and transplant-ineligible patients (based on MAIA trial) have gained an accelerated momentum for adoption into regular clinical practice. In this context, to find the most optimal non-IMID based daratumumab-combination therapy as induction, we conducted a randomized phase 2 study to evaluate the safety and efficacy for in-class transition from bortezomib to ixazomib, stratified by transplant-eligibility and R-ISS. Methods: Patients were randomized to receive Arm A [daratumumab, ixazomib and dexamethsone (DId) X 8 cycles)] or Arm B [(daratumumab, bortezomib and dexamethsone (DVd) x 3) followed by (DId x 5 cycles)] for the primary endpoint of ≥ very good partial response rate (VGPR) rate post-induction cycle 8. Several other secondary endpoints were evaluated including safety, overall repsonse rate (ORR), progression free survival (PFS) and overall survival (OS). Standard dosing schedule was used [DId: daratumumab IV 16 mg/kg on days 1, 8, 15, 22 every 28 days x 2 cycles; then on days 1, 15 every 28 days x 6 cycles and every 28 days during maintenance (or 1800 mg SC at the same schedule), ixazomib - 4 mg PO on Days 1, 8, and 15 every 28 days and dexamethasone - 40 mg PO on days 1, 8, 15 and 22 every 28 days; DVd: daratumumab IV 16 mg/kg on days 1, 8, 15, 22 every 28 days x 2 cycles; then on days 1, 15 every 28 days x 6 cycles and every 28 days during maintenance (or 1800 mg SC at the same schedule), bortezomib - 1.3 mg/m2 SC on days 1, 4, 8 and 11 every 21 day and dexamethasone - 40 mg PO on days 1, 8, 15 and 22 every 28 days]. Transplant eligible patients may receive stem cell collection and transplant after cycle 8. During the maintenance phase, patients receive DId as maintennace therapy for a total of 32 cycles. 52 subjects were enrolled at Winship Cancer Institute of Emory University between 07/2019 and 05/2022. Results: The median age was 64 years for the 48 evaluable subjects [25 (52%) in arm A, 68 (48-87) and 23 (48%) in arm B, 61 (37-80), p&amp;lt;0.25]. 56% of the cohort was male (64 vs 48%, p=0.20), 48% were black (40% vs 56.5%, p=0.245). 20.8% had t(11;14), 29.2% had 1q abnormalities, 70.8% had hyperdiploidy, 25% had complex karyotype and 10.4% were high-risk [defined as presence of del17p, t(4;14) or t(14;16)]. 38 (81%) patients underwent an autologous stem cell transplant (72% in Arm A and 90.9% in Arm B, p=1.00). The primary endpoint favored arm B (Arm A vs Arm B ≥VGPR rate: 28% vs 56.5%, p&amp;lt;0.043). Similarly, the ORR favored arm B as well (Arm A vs Arm B ORR: 76% vs 95.7%, p&amp;lt;0.062). Post transplant ≥VGPR rates and ORR were 88.9% vs 95%, p=0.458 and 100% vs 100%, p=NS, respectively. At a median follow up of 35.2 months, 80% of the patients remain progression free as shown in figure 1. The adverse event profile was similar across both cohorts (grade 3/4 events occurred in 6 (24%) vs 7 (30%) for Arm A and B, respectively, p=0.27). There was no grade 3/4 peripheral neuropathy (PN), though grade 1/2 PN were higher in Arm B. There were two secondary primary malignancy reported in Arm B (prostate adenocarcinoma, esophageal adenocarcinoma). All together the safety signals were comparable between both arms. Conclusion: This is one of the first studies showing the safety and efficacy of non-IMID based dara-combination induction therapies with in-class transition of bortezomib to ixazomib yielding higher response rates post-induction and post-transplant without compromising on the safety. 3-year PFS rate of close to 80% across both arms is for daratumumab and proteasome inhibitor combination therapy are highly encouraging and may be an alternative regimen for patients that may not tolerate IMIDs or that have a contraindication to receive IMIDs.

Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Therapy in High-Risk Newly Diagnosed Multiple Myeloma

Background: Carfilzomib, lenalidomide and dexamethasone (KRd) has been shown to be an effective induction regimen for newly diagnosed myeloma (NDMM), particularly in myeloma with high-risk (HR) features in the FORTE trial (Mina et al, Lancet Onc 2023). Here, we present a retrospective analysis in patients with HR NDMM in a real-world population from two high-volume centers, highlighting efficacy and survival outcomes in high-risk subgroups to gain a better understanding of the utility of this regimen in clinical practice. Methods: We conducted a retrospective study of patients with HR NDMM treated with KRd at Memorial Sloan Kettering (MSK) and Winship Cancer Institute from 1/1/2015 to 9/30/22. Cutoff date for analysis was 12/31/2022. HR was defined as the presence of high-risk cytogenetic abnormalities (HRCA) including +1q, del(1p), t(4;14), t(14;16), t(14;20), and/or del(17p), circulating plasma cells (cPC) ≥5%, extramedullary disease (EMD), and/or complex cytogenetics by conventional cytogenetics. Patients who received ≤1 prior cycle of a different MM regimen were included. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. Discrete patient characteristics were summarized by frequency (percentage) and continuous characteristics were summarized by median (Interquartile Range, IQR). Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier method. Association between time to event outcomes and patient's characteristics were determined by log-rank test. Univariate Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: We identified 179 consecutive NDMM patients with HR features treated with KRd at MSK (N=106) and Winship Cancer Institute (N=73). Baseline patient characteristics are listed in Table 1. The median age was 62 (IQR, 55-68) and 28% of patients were Black. There were 45 (25%), 76 (42%), 47 (26%), and 11 (6%) patients with 0, 1, 2, 3+ HRCA, respectively. A median of 5 (IQR 4-6) cycles were administered. At data cutoff, 70% of patients received upfront autologous stem cell transplant (ASCT). Best overall response rate (ORR) by the end of KRd induction was 94% for 178 response-evaluable patients, including 39% with ≥complete response (CR) and 78% with ≥very good partial response (VGPR). After a median follow-up of 41.9 (95% CI 39-45.6) months, the median PFS (mPFS) was 78.2 months (95% CI 52.5-not reached [NR]), and 2-year estimated PFS was 79% (73%-85%). Median OS (mOS) was not reached, and 2-year OS was 92% (95%CI 89%-97%). For HR subgroups based on the number of HRCA present, mPFS was 78.2 (95% CI 40.1-NR), 65.2 (43.4-NR), 55.9 (44.9-NR), and 17.5 (8.78-NR) months for patients with 0, 1, 2, 3+ HRCA, respectively, with 2-year PFS of 83% (95% CI, 73%-95%), 82% (74%-92%), 78% (67%-91%), and 46% (24%-87%), respectively (P=0.35). Median OS was NR for patients with 0, 1, and 2 HRCA and was 58.2 months (95% CI 38.8-NR) for patients with 3+ HRCA with 2-year OS of 93% (95% CI, 86%-100%), 96% (91%-100%), 89% (81%-99%), and 81% (60%-100%), respectively (P=0.13). In univariable analysis, lack of t(14;16) (HR 0.32, 95%CI 0.11-0.95; P=0.03), White race (HR 0.38, 95%CI 0.17-0.84; P=0.02), presence of ≤2 HRCA (HR 0.31, 95%CI 0.11-0.92; P=0.04) were associated with longer OS in this cohort of HR-NDMM patients treated with KRd induction. Multivariable analysis for clinical variables, including specific HRCA, number of HRCA present, age, gender, race, R-ISS stage, presence of EMD, presence of cPCs, cardiac history, and upfront ASCT did not demonstrate any single variable was a significant predictor of progression or death. Conclusion: For this real-world patient population, KRd induction was associated with high response rates and promising outcomes with best ORR of 94% and mPFS of 6.5 years for patients with high-risk newly diagnosed multiple myeloma consistent with FORTE trial data. PFS did not significantly differ among HR patients with 0, 1, 2, 3+ HRCA although mPFS for patients with 3+ HRCA was only 17.5 months. Data with maintenance therapy and longer follow-up outcomes will be presented at the meeting.

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors.

In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI. In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on patients were collected through chart review. Cox's proportional hazard model and logistic regression were applied to estimate the association with overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). The possible lead-time bias was handled in extended Cox regression models. The median age of the cohort was 68. Over one-third (35%) of patients experienced an irAE, with skin being the most frequent organ involved (12.9%). Patients that experienced at least one irAE had significantly enhanced OS (HR: 0.38, 95% CI, 0.18-0.79, P = .009), PFS (HR: 0.27, 95% CI, 0.14-0.53, P < .001), and CB (OR: 4.20, 95% CI, 1.35-13.06, P = .013). Patients who experienced dermatologic irAEs also had significantly greater OS, PFS, and CB. Of patients with advanced UC that had undergone ICI therapy, those who had irAEs, especially dermatologic irAEs, had significantly greater OS, PFS, and CB. These results may suggest that irAE's may serve as an important marker of durable response to ICI therapy in urothelial cancer. The findings of this study need to be validated with larger cohort studies in the future.

Evaluation of bleeding risk between apixaban and rivaroxaban in patients with gastrointestinal cancer.

e16323 Background: Patients with cancer are at a higher risk for developing venous thromboembolisms (VTEs), leading to further complications. The National Comprehensive Cancer Network (NCCN) guidelines currently recommend using low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) for the treatment of VTEs in oncology patients. Other trials compare DOACs with LMWH to determine the risk of bleeding. The Select-D trial found that rivaroxaban had a higher risk of bleeding in patients with gastrointestinal (GI) cancer as compared to LMWH. However, the Caravaggio trial found that apixaban had no increase of bleeding for patients with GI cancer. Due to the inherent risk of major bleeding shown in the subgroup analysis of the trials above, the guidelines recommend LMWH as the preferred agent for patients with GI cancers. At Winship Cancer Institute, DOACs are used for the treatment of cancer-associated VTE for patients with GI malignancies. The purpose of this study was to assess real-world safety outcomes of patients with GI cancer who were treated with apixaban or rivaroxaban for VTE. Methods: This study is a single-center, retrospective chart review of patients 18 years or older with GI cancer receiving treatment for VTE with either apixaban or rivaroxaban. The study looks to review bleeding outcomes in patients who started their VTE treatment from January 1, 2017 – December 31, 2021. The primary outcome of this study was to evaluate the rates of major bleeding between apixaban and rivaroxaban. Major bleeding was defined as a decrease in hemoglobin of ≥ 2g/dL over 24 hours, transfusion of ≥2 units of red blood cells, bleeding that requires surgical intervention, or bleeding at critical sites. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) defined by bleeding compromising hemodynamics, hematemesis, hemoptysis, rectal bleeding, or hematuria, VTE recurrence, and death from bleeding. Data collected to measure these outcomes included patient characteristics such as renal function, weight, primary cancer site, medication dosing, and duration and indication of treatment. Results: A total of 300 patients qualified for inclusion of this study. Of these, 89 were in the apixaban group and 211 in the rivaroxaban group. Major bleeding occurred in 3 patients in the apixaban group (3.4%) and 18 in the rivaroxaban group (8.5%). CRNMB occurred in 2 patients in the apixaban group (2.2%) and 16 patients in the rivaroxaban group (7.6%). VTE recurrence occurred in 4 patients in the apixaban group (4.5%) and 9 patients in the rivaroxaban group (4.3%). Conclusions: This is the only study to date to evaluate DOACs head to head and their bleeding risk in cancer patients. Apixaban was associated with lower rates of major bleeds and CRNMB, but relatively similar rates of VTE recurrence. The results of this study warrant consideration of using DOACs for patients with GI cancers in the upfront setting.

Characterizing outcomes in severe cytopenias by 3 months in BCMA and CD19 CAR-T cell therapies: A single institution experience.

e19504 Background: Chimeric antigen receptor (CAR) T-cell therapy is approved for treatment in relapsed/refractory diffuse large B cell lymphoma, penta-refractory multiple myeloma (MM), and acute lymphoblastic leukemia. We evaluated relapse and survival rates by 3 months (mo) in patients (pts) who received BCMA and CD19 CAR-T cell therapies. Methods: We performed a retrospective analysis of pts with RRMM and R/R Non-Hodgkin lymphoma (NHL) who received CAR-T cell therapy from 2012-2023 at the Winship Cancer Institute at Emory University. Pts who relapsed prior to 3mo were excluded. SAS was used for statistical analysis with alpha of 0.05. Grades 3/4 cytopenias were compared at day 0, 1mo, and 3mo per CTCAE criteria with each pt counted once if &gt; 1 cytopenia. Hematological recovery was defined as sustained Hgb &gt; 8, Plt &gt; 50,000, and ANC &gt; 1000 without transfusion support. Group differences were evaluated using Chi-Square or Fisher’s exact tests for categorical and ANOVA or Kruskal-Wallis for numerical variables. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method from CAR-T receipt to progression or death, or last known contact for those censored. Univariable and multivariable cox regression were performed. Results: Of 126 pts, 60 had MM and 66 had NHL. Median age at CAR-T receipt was 64yrs (range: 25-85). Fifteen pts had ECOG ≥2. Most pts were male (52.4%) and of white race (61.9%). For R/R NHL, 39.4% received tisa-cel, 33.3% axi-cel, 13.6% brexu-cel, 3.0% liso-cel and 10.6% clinical trial. For RRMM, 91.7% received ide-cel and cilta-cel (8.3%). Bridging therapy, CRS, and ICANS were not associated with severe cytopenias. Overall, 89.7% had grade 3/4 cytopenias at day 0, 54.0% at 1mo, and 34.1% at 3mo. Cytopenia rates, hematological recovery, transfusions, and infectious complications were comparable between groups. Overall, 36.5% required GCSF, 34.9% red cells, 23.0% platelets, and 2.4% TPO. In MM pts, decreased OS was seen with persistence of severe cytopenias (p = 0.009) and decreased PFS with GCSF use ≥2wks (p = 0.007). Time to ANC recovery (days) was more prolonged in MM compared to NHL pts (p = 0.039). Overall median time to recovery (days) was 8, 19, 22.5 for Hgb, ANC, and Plt respectively. On MVA for overall cohort, grade 3/4 cytopenias at 3mo were associated with decreased OS [HR 2.28, 95%CI: (1.22-4.29), p = 0.010) and PFS [HR 1.8, 95%CI: (1.09-2.98), p = 0.022]. On MVA for NHL, decreased OS [HR 2.38, 95%CI: (1.03-5.48), p = 0.043] and PFS [HR 2.11, 95%CI: (1.01-4.41), p = 0.047] were associated with 3mo grade 3/4 cytopenias but not seen in MM pts. Conclusions: We report significant rates of severe cytopenias at 3 months and a potential association with higher relapse and decreased survival rates in pts receiving BCMA and CD19 CAR-T cell therapies. These results are hypothesis generating, and more prospective studies are needed for further confirmation.

The Importance of Collaboration Elevating Cardio-Oncology Care

The Importance of Collaboration Elevating Cardio-Oncology Care

Characterizing Outcomes in Visceral Cutaneous T-Cell Lymphoma: A Single Center Retrospective Study

IntroductionVisceral involvement of cutaneous T-cell lymphoma (vCTCL) is a rare but poorly studied complication of CTCL. We aimed to assess clinical characteristics, treatment, and outcomes, associated with vCTCL at our institution. MethodsWe conducted a retrospective review of patients with vCTCL among patients with a confirmed histopathologic diagnosis of CTCL seen at the Winship Cancer Institute in Emory University. vCTCL was defined as a highest TNMB stage of 4B with extracutaneous metastatic disease (M1) pathologically confirmed or strongly clinically suspected based on imaging, symptoms, and the clinical judgment of the treating physician. Patients were selected from our CTCL database containing 656 patients from 1990 to 2022. Clinical characteristics were characterized. Clinical outcomes were measured as overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curve and univariable Cox regression analysis. ResultsTwenty-six of 656 patients with vCTCL were identified. 42.3% of patients were black. Twenty-two patients were diagnosed with MF/SS and 4 had other CTCL subtypes including pcALCL, Gamma-Delta, and Cytotoxic T-Cell Lymphoma. The median PFS and OS were 7.3 months (3.8, 11) and 12.1 months (9.9, 18.2), respectively. Median time to metastasis from initial diagnosis was 12.1 months. The most common M1 sites were liver (19.2%) and lung (42.3%). M1 sites outside of liver or lung were associated with inferior OS (HR 8.9, 95%CI: 2.7-29.5, P-value <.001) and PFS (HR 4.3, 95%CI: 1.44-12.7, P-value = .009). No treatments or baseline factors were associated with improved survival. ConclusionOur retrospective study confirms therapy resistance and dismal outcomes among patients with vCTCL.