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AbstractObjectivesThirty‐five states, including Florida, now cover cell‐free DNA (cfDNA) screening of fetuses for all pregnant patients enrolled in state public insurance programs. We interviewed Black and Hispanic obstetric patients at a safety net clinic in Florida shortly after the state rolled out cfDNA as a first‐tier screening method for publicly insured patients.MethodsBlack and Hispanic patients receiving prenatal care from a prenatal or maternal fetal medicine clinic at a federally qualified health center in Jacksonville, FL were invited to participate in a qualitative interview in English or Spanish to explore experiences and perceptions of prenatal cfDNA screening. Participants were recruited following their first prenatal visit when cfDNA is typically introduced. Interview transcripts were qualitatively analyzed for iterative themes based on principles of grounded theory.ResultsOne hundred Black and Hispanic patients (n = 51 non‐Hispanic Black, n = 43 Hispanic, n = 3 Hispanic Black, n = 3 Not Reported/Other) completed an interview. Participants described minimal opportunity for pre‐screening counseling and limited health literacy about cfDNA or its uses. Some believed that cfDNA could positively impact pregnancy health. Many were unsure if they had received cfDNA even though they were aware of the information provided by it. Most participants expressed an interest in cfDNA as a means for early detection of fetal sex and as an additional indication of general fetal health.ConclusionsPatient experiences indicate limited informed consent and decision‐making for cfDNA, discordant with professional guidelines on pre‐screen counseling. Our findings suggest that there should be additional investment in implementing cfDNA in safety net settings to ensure that patients and providers receive the support necessary for effective patient counseling and follow‐on care for the ethical implementation of cfDNA.

Background:Ibrutinib is approved in Europe and the US for the treatment of Waldenstrom macroglobulinemia (WM) with a median progression‐free survival (PFS) measured on several years. As PFS is commonly used for drug approval by regulatory entities, there is an unmet need of reliable surrogate markers for PFS that could help accelerating such process. This is of importance with novel BTK inhibitors currently in clinical trials.Aims:We hypothesized that the depth of response at 6 months can be predictive of PFS in patients with WM treated with the BTK inhibitor ibrutinib.Methods:We evaluated our hypothesis in two separate cohorts of WM patients treated with ibrutinib. The learning cohort was composed by participants of two prospective clinical trials at Dana‐Farber Cancer Institute (DFCI), Memorial Sloan Kettering Cancer Center and Stanford Cancer Center. The validation cohort was composed by consecutive WM patients treated with ibrutinib off clinical trial at DFCI and Mayo Clinic. Categorical responses at 6 months were assessed based on criteria from the 6thInternational Workshop for WM. PFS6 was defined as the time from the 6‐month response assessment until progression of disease or death from any cause. PFS6 curves were generated using the Kaplan‐Meier method and compared using the log‐rank test. Cox proportional hazard regression models were fitted for PFS6. Pvalues <0.05 were considered statistically significant.Results:The learning and validation cohorts were composed by 92 and 190 WM patients treated with ibrutinib, repsectively. There were no statistical differences between cohorts with regards to age, sex, serum IgM level, hemoglobin level, bone marrow involvement, prior treatment status, and MYD88 and CXCR4 mutational status (p>0.05 for all variables). The rates of partial response (PR) or better at 6 months in the learning and validation cohorts were 63% (54/86) and 72% (114/159), respectively (p = 0.15). The median PFS6 was not reached in the learning cohort and was 53 months (95% CI 44‐not reached) in the validation cohort. In the learning cohort, the median PFS6 for patients who attained a PR or better at 6 months was not reached, while for the patients who did not attained PR at 6 months was 48 months (95% CI 33‐not reached). The 3‐year PFS rate for patients who attained a PR or better at 6 months was 83% (95% CI 68–91%), while for patients who did not attained PR at 6 months was 58% (95% CI 33–76%) (Figure, left, log‐rank p = 0.02). Attaining PR or better at 6 months was associated with a hazard ratio (HR) or progressing or dying of 0.37 (95% CI 0.16–0.87; p = 0.02).In the validation cohort, the median PFS6 for patients who attained a PR or better at 6 months was 53 months (95% CI 44‐not reached), while for the patients who did not attained PR at 6 months was 32 months (95% CI 22‐not reached). The 3‐year PFS rate for patients who attained a PR or better at 6 months was 79% (95% CI 67–87%), while for patients who did not attained PR at 6 months was 50% (95% CI 26–70%) (Figure, right, log‐rank p = 0.04). Attaining PR or better at 6 months was associated with a hazard ratio (HR) or progressing or dying of 0.46 (95% CI 0.22–0.98; p = 0.04). Age, sex, serum IgM level, hemoglobin level, bone marrow involvement and prior treatment status were not prognostic of PFS6 in both cohorts.Summary/Conclusion:Attaining a PR or better at 6 months to ibrutinib is associated with longer median PFS and higher rates of 3‐year PFS in WM patients. Depth of response at 6 months could serve as a surrogate for PFS in clinical trials evaluating BTK inhibitors in WM patients.image

ImportanceIncarcerated patients admitted to the hospital face threats to their rights to privacy and self-determination in medical decision-making. Little is known about medical decision-making processes for hospitalized incarcerated persons who lack decisional capacity.ObjectiveTo characterize the prevalence of incapacity among hospitalized incarcerated patients and describe the decision-making processes, including who served as surrogate decision-makers, involvement of prison employees in medical decisions, and ethical concerns emerging from the patients’ care.Design, Setting, and ParticipantsRetrospective descriptive and qualitative study of medical records for all patients admitted from prison for at least 24 hours between January 1, 1999, and September 1, 2019, at a large Midwestern academic medical center. Data analysis was performed from March 15, 2021, to December 14, 2022.Main Outcomes and MeasuresPrevalence of prison-to-hospital admissions for patients with a loss of capacity and characteristics of medical decision-making.ResultsDuring the 20-year study period, 462 patients from the prison were admitted to the hospital, totaling 967 unique admissions. Of these, 131 admissions (14%) involved patients with a loss of capacity and 43 admissions (4%, representing 34 unique patients) required surrogate decision-making. Ten of these patients had advance directives. Surrogate decision-makers often faced decisions about end-of-life care (n = 17) or procedural consent (n = 23). A family member was identified as surrogate decision-maker in 23 admissions. In 6 cases with a kindred surrogate, additional consent was requested from a prison employee. In total, prison employees were documented as being present during or participating in major medical decisions for half of the admissions. Five themes emerged from thematic analysis: uncertainty and misinformation about patient rights and the role of prison employees in medical decision-making with respect to these two themes, privacy violations, deference to prison officials, and estrangement from family and friends outside of the prison.Conclusions and RelevanceIn this first in-depth description, to date, of decision-making practices for hospitalized incarcerated patients lacking decisional capacity, admissions of these patients generated uncertainty about their rights, sometimes infringing on patients’ privacy and autonomy. Clinicians will encounter incarcerated patients in both hospital and clinic settings and should receive education on how to support ethically and legally sound decision-making practices for this medically vulnerable population.

Introduction: MDS are primarily diseases of the elderly, with median age at diagnosis of 72 years. Focused data on clinical and molecular characteristics, as well as outcomes, in younger pts under age 60 years are limited. We conducted this multicenter retrospective study to describe pt characteristics, cytogenetic and molecular profiles, treatment modalities, and outcomes in younger pts with MDS, including adolescent and young adults (AYA). Methods: The study included pts diagnosed with MDS between 2002-2023 at 7 academic centers. We compared baseline characteristics, treatment, and outcomes of AYA (18-39 years) and younger adult (YA) pts (40-59 years). Responses were assessed using the modified IWG 2006 response criteria which included complete remission (CR), marrow CR (mCR), and hematologic improvement (HI). Wilcoxon rank sum test and Fisher's exact (and Chi-square) test were used to compare pt and disease characteristics for continuous and categorical variables, respectively. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using log-rank test. Results: A total of 173 pts were identified (AYA, N=50; YA, N=123). Median age at diagnosis was 50 years (range, 18-59), with 51% females. Baseline characteristics are shown in Table 1. Therapy-related MDS (t-MDS) was observed in 40 pts (23%) with the remaining classified as de novo MDS (N=133; 77%). Inherited bone marrow failure syndromes were documented in 15 pts (9%), with Shwachman-Diamond Syndrome (N=4) and Fanconi anemia (N=4) being the most frequent. Using the WHO 2016 classification, the most common subtypes of MDS in both the AYA and YA cohorts were MDS with multilineage dysplasia (38% vs 19%), MDS with excess blasts-2 (MDS-EB) (24% vs 29%), and MDS-EB-1 (16% vs 20%). Similarly, using the WHO 2022 classification, the most common subtypes were MDS with low blasts (50% vs 21%), MDS with increased blasts-2 (MDS-IB-2) (24% vs 24%), and MDS-IB-1 (16% vs 18%). Stratifying pts using the IPSS-R cytogenetic (CG) risk group, the most common CG risk category identified was good CG (34% vs 52%, p=0.012). Poor/very poor CG were present in 34% and 37% of the AYA and YA groups, respectively. STAG2 and NRAS mutations occurred more frequently in the AYA pts compared to the YA group, while the YA cohort was enriched for the following mutations: TP53, DNMT3A, SF3B1, SRSF2, and TET2 (Figure 1). In the AYA population, 18 pts (38%) had very low/low, 10 (21%) intermediate, and 20 pts (42%) had high/very high risk MDS using IPSS-R. In the YA population, 32 pts (26%) had very low/low, 32 (26%) intermediate, and 57 pts (47%) had high/very high risk MDS using IPSS-R. Twenty-seven percent of pts with very low to intermediate-risk MDS using IPSS-R were upstaged to moderate high to very high-risk MDS using IPSS-M. The majority of pts (AYA: 75%; YA: 63%, p=0.5) were transfusion independent at baseline. Single-agent hypomethylating agents were the most frequently used frontline therapy, used in 17 AYA pts (34%) and 58 YA pts (48%), with more AYA pts receiving upfront allogeneic stem cell transplantation (Allo-SCT) compared to YA pts (28% vs 5%). After frontline therapy (Table 1), an additional 14 AYA (28%) and 52 YA (42%) pts received Allo-SCT. In pts with IPSS-R intermediate to very high-risk, response rates (HI+CR+mCR+mCR with HI) to frontline therapies were 46% and 54.5% in the AYA and YA groups, respectively. After median follow-up of 24 months [range, 1-218], median OS was numerically longer in the AYA versus YA group (155 vs 53 months, p=0.2). AML transformation occurred in 24% and 20% of the pts in the AYA and YA groups, respectively. Median OS was significantly longer in de novo compared to t-MDS pts (56 vs 27 months, p=0.03). Median OS among Allo-SCT compared to non-SCT pts were not reached vs 155 months ( p=0.9) in the AYA group and 53 vs 54 months ( p=0.4) in the YA group. IPSS-R (very low+low vs intermediate vs high+very high) was able to distinguish differences in OS in the YA (133 vs 53 vs 17 months, p=0.0002) and AYA (155 vs not reached vs 18 months, p=0.006) pts, with the exception of the intermediate-risk group in the AYA cohort. Conclusions: In this study, d e novoMDS was seen in the majority of younger pts with MDS (both AYA and YA). Mutations in STAG2 and NRAS were more common in the AYA pts, while YA pts had MDS more enriched for TP53, DNMT3A, TET2 and splicing mutations. This study is still ongoing with a plan to compare the abovementioned groups to older pts (≥60 years) with MDS.

Abstract Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis but evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. To understand Black women’s perspectives on HBOC genetic testing and potential factors influencing this decision, we conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer. Participants were recruited via the networks of patient support organizations and sororities as well as at a family medicine safety net clinic in Jacksonville, FL. Participants frequently expressed a lack of awareness about their family cancer history; many cancer patients stated that they only became aware of extensive family history upon their own diagnosis. Lack of family history sharing was attributed to a culture of silence around medical issues and a desire to protect family members from difficult information. However, most participants indicated a strong desire to understand their own risk of HBOC and were interested in genetic testing. Participants with a personal diagnosis were motivated to undergo HBOC genetic testing to reduce the risk for future generations. Clinical experiences with the offer of HBOC genetic testing were variable, with a few expressing that they had to make repeated inquiries from a provider to understand the relevance of the test to their own health. These findings suggest that investigation into alternative clinical modalities to collect family health history may be beneficial to identify Black women who meet NCCN Guidelines for HBOC testing. In contrast to the literature suggesting hesitancy for HBOC genetic testing, many participants perceived genetic results as having a positive impact for their medical decision-making and family's health. The development of patient materials and provider education on cultural and social factors that influence the uptake of HBOC genetic testing is also needed. Citation Format: Kirsten A. Riggan, Michele Halyard, Sarah E. James, Marion Kelly, Daphne Phillips, Megan A. Allyse. Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing [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 A067.

Objectives In 2018, the Healing Emotional Lives of Peers (HELP) Program was implemented at Mayo Clinic Rochester to guide healthcare professionals (HCPs) after a second victim experience, such as adverse patient events or medical errors. The HELP program was expanded to all HCPs in response to the anticipated stressors of the COVID-19 pandemic. This article aims to describe the rapid expansion of the peer support program and evaluate the effectiveness of peer support provided to affected colleagues (ACs). Methods Quantitative data collected from workshop evaluations, activations, and associated metrics (TPS Self-Assessment, Encounter Form, and AC Self-Assessment) were summarized through standard descriptive statistics using SAS version 9.4 software. Open-ended responses were qualitatively analyzed for iterative themes about the HELP program and associated workshops. Results Between April 2020 and December 2021, 22 virtual workshops to train peer supporters were conducted with 827 attendees. Of these, 464 employees completed the workshop evaluation. A total of 94.2% rated the workshop as excellent or very good. Participants perceived the workshop to be highly effective and felt more prepared to support ACs. Between May 2020 and December 2021, 247 activations were submitted through the HELP Program’s intranet Web site and peer support was requested for 649 employees. Of the 268 TPS Self-Assessments, 226 (84.3%) felt that they provided helpful support to an AC. One hundred ACs evaluated support received, with 93% being “extremely” or “very satisfied.” Affected colleagues appreciated having a TPS provide judgment-free support. Conclusions The HELP Program promotes a culture of safety by helping HCPs process traumatic events. To effectively meet the needs of patients, healthcare organizations need to prioritize the well-being of their employees through interpersonal support.

Abstract In the development of various strategies of anti-CD19 immunotherapy for the treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant treatment with tafasitamab and CART19 showed major CD19 binding competition, which led to CART19 functional impairment. However, when CD19+ cell lines were pretreated with tafasitamab overnight and the unbound antibody was subsequently removed from the culture, CART19 function was not affected. In preclinical in vivo models, tafasitamab pretreatment demonstrated reduced incidence and severity of cytokine release syndrome and exhibited superior antitumor effects and overall survival compared with CART19 alone. This was associated with transient CD19 occupancy with tafasitamab, which in turn resulted in the inhibition of CART19 overactivation, leading to diminished CAR T apoptosis and pyroptosis of tumor cells.