Citations

Background: Bendamustine and rituximab (BR) is a standard-of-care first-line (1L) therapy for older or unfit patients with mantle cell lymphoma (MCL). The SHINE trial compared BR with rituximab maintenance plus ibrutinib vs placebo in patients ≥65 years old and showed that the ibrutinib arm had significantly improved progression-free survival (PFS; median 80.6 vs 52.9 months) but similar overall survival (OS; 57% vs 55% at 7 years) compared to the placebo arm. Whether sequential treatment with BR in 1L and a Bruton's tyrosine kinase inhibitor (BTKi) in second-line (2L) can result in a similar cumulative PFS compared to 1L BR plus BTKi combination therapy is unknown. To provide insight to this question, we modeled observational data to evaluate MCL outcomes after 1L BR and 2L BTKi therapy in the BTKi era. Methods: Patients with MCL who received 1L BR with or without rituximab maintenance in 2014-2020 at one of the 27 participating centers were included. Exclusion criteria included participation in the SHINE or ECHO trials, any additional 1L therapy other than BR (with or without rituximab maintenance), and stem cell transplant consolidation after 1L BR. Baseline characteristics, treatment, and follow-up data were abstracted by chart review. Event-free survival (EFS) was defined as time from index line treatment start to the first event (progression, relapse, retreatment, or death). OS was defined as time from index line treatment start to death. Using an intention-to-treat (ITT) framework, EFS2 was defined as time from 1L BR start to progression, relapse, or retreatment following 2L BTKi treatment or death. Patients who received a non-BTKi treatment at 2L were censored for EFS2 at 2L treatment start; living patients without an event following 1L BR or 2L BTKi were censored for EFS2 at last follow-up. Results: A total of 618 patients with MCL who received 1L BR in 2014-2020 were included. The median age was 71 (IQR 65-76) years, and 447 (72%) were male. 59 (11%) patients had an ECOG PS ≥2, 566 (93%) had stage III-IV disease, and simplified MIPI was low in 105 (21%), intermediate in 200 (39%), and high in 202 (40%) patients. The median follow-up following 1L BR start was 57.4 (95% CI 53.8-63.2) months. Response data were available in 580 patients, and the best ORR was 92% (79% complete response [CR] and 13% partial response [PR]). 258 (42%) patients received rituximab maintenance. As of last follow-up, 255 patients were alive and in remission after 1L BR, 92 patients died without 2L therapy, and 271 patients received a 2L therapy. The median EFS was 34.1 (95% CI 31.0-40.0) months. The median OS was 97.8 (95% CI 81.2-NA) months, the 5-year OS rate was 58.6% (95% CI 54.4-63.2), and the 7-year OS rate was 56.7% (95% CI 52.4-61.5) (Fig 1). Among the 271 patients who started a 2L treatment, 203 (75%) received a BTKi at 2L - 101 (50%) ibrutinib, 76 (37%) acalabrutinib, and 26 (13%) zanubrutinib. The median follow-up following 2L BTKi start was 38.5 (95% CI 31.3-45.1) months. Response data were available in 171 patients, and the best ORR was 64% (36% CR, 28% PR). The median EFS was 10.7 (95% CI 7.7-14.0) months, and the median OS was 24.8 (95% CI 17.3-33.1) months with 2L BTKi therapy (Fig 2). By ITT analysis, the median EFS2 following 1L BR and 2L BTKi was 72.1 (95% CI 56.7-97.8) months (Fig 1). A subset analysis of patients aged ≥65 years (n=471; 198 [42%] received rituximab maintenance) showed similar results. The median EFS with 1L BR was 32.7 (95% CI 29.1-36.3) months. The median OS was 81.5 (95% CI 65.0-NA) months, and the 7-year OS rate was 53.3% (95% CI 48.3-58.7). 208 patients received a 2L therapy, 163 (79%) with a BTKi. The median EFS was 11.5 (95% CI 7.6-15.8) months, and the median OS was 21.0 (95% CI 14.0-29.6) months with 2L BTKi therapy. By ITT analysis, the median EFS2 following 1L BR and 2L BTKi was 58.0 (95% CI 50.2-77.0) months. Conclusion: In this multicenter retrospective study, initiation of 1L BR (with or without rituximab maintenance) resulted in a 7-year OS of 57%. Median EFS2 for sequential 1L BR and 2L BTKi was 72.1 months. In context, the SHINE study reported a median PFS of 80.6 months in the BR (with rituximab maintenance) plus ibrutinib arm and a 7-year OS of 57% in the ibrutinib arm and 55% in the placebo arm, where 39% of patients received a BTKi in 2L. Within the constraints of observational data, our results provide support for sequential use of BR in 1L and BTKi in 2L for patients with MCL.

Background: Pediatric patients (pts) with low-risk cHL achieve high cure rates with standard chemo. However, those with a SER to front-line chemo are at higher risk of relapse than pts with a rapid early response (RER). Current treatment options are also associated with long-term toxicities such as secondary malignancies, cardiovascular disease, and pulmonary and gonadal toxicity. Novel treatment approaches are needed to optimize outcomes while minimizing long-term toxicity. KEYNOTE-667 (NCT03407144) is an open-label, phase 2 study that included an analysis of safety and efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) induction in pediatric pts with low-risk cHL followed by consolidation with pembro plus AVD and involved-site radiotherapy (ISRT) and pembro maintenance in those with SER to front-line ABVD. We present an interim analysis of pts with low-risk cHL enrolled in this trial. Methods: Eligible pts were 3-25 y old and had newly diagnosed stage IA, IB, or IIA cHL without bulky disease, measurable disease per investigator assessment, and a Lansky Play-Performance Scale ≥50 (aged <16 y) or a Karnofsky score of ≥50 (aged ≥16 y). Pts initially received 2 cycles of induction with ABVD. Response was then assessed by PET/MRI/CT (early response assessment). Pts with RER received nonstudy therapy per treating physician. Pts with SER (Deauville score [DS], 4 or 5) received consolidation with pembro 2 mg/kg up to 200 mg IV Q3W (3-17 y) or 200 mg IV Q3W (18-25 y) in combination with 2 cycles of AVD followed by a late response assessment (LRA) with PET/MRI/CT. All pts with a SER then received ISRT (21.6 Gy for pts with a complete PET response [DS, 1-3]; 30.6-36 Gy for pts with a partial PET response [DS, 4 or 5]) plus maintenance pembro Q3W for up to 17 cycles. Primary end point was ORR by blinded independent central review (BICR) per Cheson 2007 IWG criteria in pts with SER determined at any time after starting pembro and before start of new anticancer therapy. Secondary end points included rate of PET negativity after consolidation, EFS, OS, and safety. Results: 73 pts with low-risk cHL were enrolled, 9 of whom had SER to ABVD induction. 64 pts had a RER and received nonstudy treatment. At data cutoff (March 1, 2023), 2 of 9 pts (22%) with SER had completed consolidation and maintenance therapy, 5 (56%) were ongoing, and 2 (22%) had discontinued, both because of complete response. Median time from enrollment to data cutoff was 8.7 mo (range, 2.2-32.9). Median age was 16 y (range, 7-20), 5 pts (56%) were male, 2 (22%) had Ann Arbor stage I disease, and 7 (78%) had Ann Arbor stage II disease. Pts with SER had received a median of 8 doses of pembro (range, 1-17); median time on pembro was 4.8 mo (range, <0.1-11.3). Of 9 pts who received consolidation therapy with pembro plus AVD, 6 (67%) had a LRA (3 are still in consolidation and have not reached the LRA timepoint), of whom 3 (50%) were PET negative by BICR (2 [33%] were PET negative by investigator review). Of 73 pts who received ABVD induction, 66 (90%) had an AE regardless of causality. 33 pts (45%) experienced grade 3/4 AEs, most commonly (≥10%) neutrophil count decreased (n = 19; 26%) and neutropenia (n = 9; 12.3%). One pt experienced grade 4 febrile neutropenia. Twelve pts (16%) had serious AEs. No pts discontinued treatment or died because of AEs. Treatment-related AEs due to ABVD induction occurred in 59 pts (81%), with grade 3/4 events in 31 (42%). Of the 9 pts with SER to ABVD induction who received consolidation and maintenance therapy, 7 (78%) experienced an AE regardless of causality. Two pts (22%) had grade 3/4 AEs. No serious AEs were reported during consolidation and maintenance therapy, and no pts discontinued treatment or died because of AEs. Treatment-related AEs occurred in 6 pts (67%) who received consolidation and maintenance therapy; with grade 3/4 events in 2 pts (22%). Six pts (67%) experienced AEs related to pembro; most commonly (≥3 pts) anemia, nausea, vomiting (n = 3 each [33%]). Two pts experienced grade 3/4 AEs related to pembro (vomiting, white blood cell count decreased). One pt (11%) experienced an immune-mediated AE (grade 2 hyperthyroidism). Conclusion: Early results from the low-risk cHL cohort of KEYNOTE-667 suggest that induction therapy with ABVD and consolidation with pembro plus AVD had a manageable safety profile. Among the relatively small number of pts with a SER to ABVD, 50% with a LRA had a PET-negative response by BICR and received a reduced dose of RT.

Abstract While the Joint Commission requires health care organizations (HCOs) to have plans for addressing health disparities effective in July, 2023, many HCOs were frustrated by their inability to consistently and accurately capture and apply social determinants of health (SDH) data to clinical care and research in the health ecosystem. Dr. Young Juhn, Director of the Mayo Clinic Precision Population Science Lab (PPSL) and his team, developed and applied a standardized individual-level SDH measure derived from publically available individual housing features known as HOUSES Index. This validated individual-level SDH measure is now available across all 50 states through the HOUSES Cloud Platform that is patient-contact free, automated, and HIPAA compliant. The Houses Index can be made available in real time through electronic health records (EHR’s) enabling clinicians and their patients to make a shared decision for treatment options with SDH taken under consideration. In addition, HOUSES Index is a valuable research tool for risk stratification for cancer outcomes, improving (and auditing) artificial intelligence (AI) model performance, assessing longitudinal change of SDH and geospatial patterns of outcomes, and monitoring proper representation of underserved populations in cancer research. In this presentation, Dr. Young Juhn will discuss the current challenges for capturing SDH data in health care, the HOUSES Index and Platform as the solutions and its implications on cancer care and research. Citation Format: Young Juhn. The HOUSES Platform for precision cancer care and research: A cloud-based nationwide measure for next generation patient-level social determinants of health [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA043.

Abstract Introduction: The relentless surge of prostate cancer rates is rapidly alarming public health officials, leaving a trail of shattered hopes among Black men in the United States. This toll reduces mortality for this population, the urgent need for effective solutions becomes more apparent. Survivorship care plans (SCPs) emerge as a beacon of hope, holding the potential to transform the provision of care. Within this tool lies the encapsulation of vital cancer-related information, passed from the oncology team to the resilient survivor and their primary care physician. However, despite the unwavering support of national governing bodies, a disheartening reality persists for Black male survivors, who never access these life-saving plans. The study purpose was to identify receipt of SCPs and the preferred communication delivery of health information among Black prostate cancer survivors. Methods: Utilizing a grounded theory approach, our study delved into the experiences of a convenience sample of seven Black male prostate cancer survivors. In-person and telephone-based semi-structured interviews we sought to unravel unique narratives. The research inquiries used open-ended questions (1) knowledge, awareness, and understanding of SCPs; (2) interactions with medical professionals; and (3) preferred methods of communication of healthcare information. Employing a line-by-line descriptive force coding method, we extracted pertinent statements by open and axial coding to generate specific codes to encapsulate information collected from an underserved population. Results: Thorough analysis revealed several distinct themes pertaining to survivorship care plans and preferred communication styles. The relevant findings were a lack of SCPs knowledge, an absence of post-treatment care, the profound influence of faith and family support, and the value of group settings. Despite receiving education on treatment, survivors expressed a sense of being left adrift, as if their medical professional team had failed to provide them with a clear roadmap for their survivorship journey. In the absence of proper guidance, survivors resorted to considering pre-treatment risk assessments as a makeshift substitute for a comprehensive survivorship care plan. Conclusion: The impact of our study’s findings resonates deeply, revealing a startling reality: Black male survivors in our sample possessed a distressing lack of knowledge about the post-treatment phase of survivorship. Instead, they relied on the support of their spouses or fellow survivors with whom they connected during treatment sessions. The removal of government mandates aimed at promoting SCPs likely contributes toward a disheartening knowledge disparities among many Black men, leaving them without clear guidance regarding the crucial phase of aftercare. Armed with this data, we have the opportunity to drive change and enhance the development of culturally tailored, interactive care plans specifically designed to support Black male survivors after they conquer prostate cancer treatment. Citation Format: Dottington Fullwood, Charles Waldon, Carol Thomas, Mary Ellen Young, Shannon Pressey, Folakemi T. Odedina, Brandon Snipe, Isela Villasenor. Unsilenced strength: Survivorship perspectives from Black prostate cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B013.

Abstract Background: Equitable representation in research remains a critical issue. Barriers to diversity in research have been identified across personal, provider, and health systems levels. To achieve true health equity, investigators must creatively collaborate with community stakeholders for increased education and partnership. The Mayo Clinic Community Engagement in Research and Clinical Trial (CERCT) curriculum was developed in 2022 to improve the inclusivity and diversity of frontline community-based health workers in research, including community health workers (CHWs), pharmacy technicians, health advocates, and citizen scientists. Aim: The CERCT curriculum was designed to empower and improve the skills necessary for engaging members of the communities about research and clinical trial (CT) participation. Aims for this project include beta pilot training of key community stakeholders in underserved minoritized communities, evaluating the efficacy of CERCT modules through increased recruitment into the Mayo Clinic Florida Community Research Registry; and increased diverse representation in research studies. Methods: This project will train community health advocate cohorts in educating the community on the importance and benefits of participating in research and CT and how to effectively communicate that information within their circles of influence both at work and where they live. Five community health advocate cohorts in Florida counties will be trained through 2-hour online modules, taken at their leisure. Results: Eight online module units will be utilized for beta training of CHWs, pharmacy technicians, health advocates and citizen scientists. Modules include explaining importance of biomedical research and CT; recognizing the different types of research and human participation studies; describing the importance/need of increased representation and inclusion; identifying how the safety, welfare, and well-being of participants are protected at every step in the research process; understanding the role of healthcare providers in research participation; learning communication strategies and tools to raise awareness of CT; examining at an in-depth level the informed consent process and conversation with potential participants; and learning to build trust and address common patient concerns and questions. Efficacy will be assessed via community enrollment in the Mayo Clinic Community Research Registry. Conclusion: Currently, community health workers and pharmacy technicians are an underexplored avenue for disseminating CT education and research inclusivity. The development and beta testing of a curricula specifically created for key community stakeholders who may or may not work in the healthcare or research fields seeks to empower those members with the education to inform their communities and increase representation in science. Designed for increasing education, dispelling common misperceptions, and an easy format, these modules are expected to increase the reach of research into historically underrepresented communities. Citation Format: Jennifer M. Crook, Opeyemi Bolajoko, Barbara Greguson, Gwen Boe, Karen Young, Katrina Croghan, Folakemi Odedina. Increasing the arm of research by finding and training key community stakeholders: The Mayo Clinic "Community Engagement in Research and Clinical Trial (CERCT)" curriculum phase 2 [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A086.

Abstract Background: The increasing number of African immigrants in the United States has contributed to the diversity of the country's Black population. However, there is limited research on the impact of immigration, particularly regarding chronic diseases like cancer, within the sub-Saharan African immigrant (SSAI) community. To address this gap, this study aimed to explore cultural factors among SSAIs to better understand the drivers of health disparities in prostate cancer outcomes. Methods: A qualitative approach using grounded theory was employed for this study. Participants were purposefully recruited to reflect the cultural diversity among SSAIs. Recruitment occurred at health fairs, community events and by snowball approach. In-depth interviews were conducted with 16 participants, including prostate cancer survivors. Nine participants have lived in the US for at least 10 years. The average age of participants was 51 years. Country of birth for study participants include, Nigeria, Ghana, Cameroon, Kenya, and Ethiopia. Interviews were transcribed, verified, and de-identified then imported into NVivo 12 software. Four research team members, three of them African immigrants, performed open and axial coding, with consensus on the emerging findings. Results: This study identified several key cultural factors influencing SSAI men’s health behaviors. These factors include the perception of cancer in their country of birth, the low priority given to preventative care in their country of origin, and reluctance to embrace a Westernized diet, the perception of cancer in their country of origin as a death sentence, viewing cancer as a spiritual/religious attack, and associating cancer with affluence. In addition, these cultural factors made participants hesitant to discuss cancer, relying on religion for healing instead of medical care, and seeking healthcare only for cure. Conclusion: This study illuminates key cultural factors among SSAI men that influence their health-seeking behaviors. These findings highlight the need for culturally tailored behavioral interventions to address these factors and improve health outcomes within this understudied population. Citation Format: Ernest Kaninjing, Motolani Ogunsanya, Kaitlin Van Voorhis, Gladys Asiedu, Assata Kokayi, Rae Walker Brennan, Mary Ellen Young, Folake Odedina. The influence of cultural factors on health-seeking behaviors regarding prostate cancer among African immigrant men in the United States [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A070.

Abstract Background: Sub-Saharan African immigrant (SSAI) men constitute one of the fastest-growing immigrant populations in the United States and a large heterogeneous group in cancer survivorship. Yet research has ignored decision making about health and behavioral risk factors among SSAI communities. Intersecting acculturation and culture-specific perceptions about cancer screening within decision-making frameworks may be an essential step towards developing meaningful interventions for immigrant men’s healthcare. Objectives: This study aimed to gain insight into cancer-related beliefs and health decision-making practices among sub-Saharan African immigrant men. Methods: A qualitative design intersecting grounded theory analysis was employed using 16 semi-structured, in-depth individual interviews with SSAI men residing in Georgia and Florida. Participants were recruited from health fairs, community events, and by snowball effect. The average age of participants was 51 years with country of birth including Cameroon, Ethiopia, Ghana, Kenya, and Nigeria. An interview guide was prepared with emphasis on SSAI’s perspectives on lifestyle factors for cancer and decision making about cancer screening. Data were audio-recorded, transcribed, and analyzed using open, inductive, and axial coding via NVivo 12 qualitative data analysis software. Results: Findings identified key cultural factors impacting barriers to and facilitators of SSAI men’s decision-making processes and health-seeking behaviors. Most participants making positive decisions reflected on intercultural health practices made in collaboration with clinicians, significant others and community partnerships. Most participants with negative decisions tended to consider socio-cultural barriers and shortcomings in US health-care system. Participants’ preventative care decisions about cancer screening differed. Conclusions: This qualitative study illuminated key cultural factors among SSAI men that influenced their decision making about cancer screening and health-seeking behaviors. Future research should investigate longitudinal and quantitative studies to test decision-making outcomes. Funding Source: This study is funded by the National Institute on Minority Health and Health Disparities (1R15MD017012-01A1). Keywords: Cancer health disparities, Decision-making, Immigrant men, Intersectionality, Qualitative study Citation Format: Assata Kokayi, Gladys Asiedu, Kaitlin Van Voorhis, Rae Walker, M.E. Young, Folakemi Odedina, Motolani Ogunsanya, Ernie Kaninjing. Intersecting acculturation and decision making about cancer screening among sub-Saharan African immigrant men: A qualitative study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A062.

We describes the development of a poly-lactic-coglycolic acid (PLGA) nanoparticle-based system for conjugation of targeting peptides to PLGA nanoparticles and delivery of the therapeutic gene SOX9 to damaged astrocytes in a mouse stroke model.

Abstract The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear. With insights from three independent clinical cohorts of PASC patients with abnormal lung function and/or viral infection-mediated pulmonary fibrosis, we established a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. By employing a combination of spatial transcriptomics and imaging, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to the fibroproliferation in respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8+ T cell macrophage interactions in maintaining Krt8hi transitional and ectopic Krt5+ basal cell progenitors, thus impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8+ T cell derived IFN-γ and TNF stimulated lung macrophages to chronically release IL-1β, resulting in the abnormal accumulation of dysplastic epithelial progenitors and fibrosis. Notably, therapeutic neutralization of IFN-γ and TNF, or IL-1β after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC. Moreover, in contrast to other approaches requiring early intervention, we highlight therapeutic strategies to rescue fibrotic disease in the aftermath of respiratory viral infections, addressing the current unmet need in the clinical management of PASC and post-viral disease.