Das, Devika

68 Background: While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their high cost and limited global supply pose major challenges. Optimizing ICI dosing to achieve a minimum effective dose that has shown to maintain clinical benefit may be a potential solution with significant savings to the health system. We investigated potential savings in Medicare that could be attained from alternative ICI dosing. Methods: We conducted a literature review including original Phase 1/2 trials describing the minimal effective dose of three commonly used ICIs: Pembrolizumab (P), Nivolumab (N) and Atezolizumab (A). Alternate dosing strategies based on existing data for Pembrolizumab (2 mg/kg), Nivolumab (1 mg/kg) and Atezolizumab (4 mg/kg) were proposed. Publicly available CMS data on Medicare Part B expenditure for these therapies was utilized to obtain average cost per dosage unit, mg/dosage unit, and number of Medicare beneficiaries between 2018-2021. Average cost per dose and total cost per ICI was calculated based on current FDA approved dosing and alternate dosing strategies. Results: The average wholesale cost per fixed dose for P (200 mg), N (480 mg), and A were $9,242.00, $12,460.80, and $8,616.00, respectively. Implementing the proposed alternate dosing strategies led to a substantial reduction in drug costs: P ($7,393.60), N ($2,076.80), and A ($2,297.60). The ensuing cost savings were calculated based on the annual number of Medicare beneficiaries. From 2018-2021, the average total savings were estimated to be $95,545,182 for Pembrolizumab, $294,734,264 for Nivolumab, and $62,937,582 for Atezolizumab (Table). The cumulative average total cost savings from 2018-2021 exceeded $453 million. Conclusions: We demonstrate potential savings in Medicare with implementation of an alternative ICI dosing strategy. Our study underscores an urgent need to better understand clinical efficacy and cost savings from a patient perspective, and feasibility from a regulatory standpoint. This perspective may hold considerable global implications, providing a roadmap for cost-effective care in the domain of immunotherapy. [Table: see text]

9037 Background: The clinical outcomes for patients with NSCLC remain suboptimal despite recent advancements in anti-PD-1/PD-L1 immunotherapies. Thus, identification of rational combinations of novel immune checkpoint (IC) strategies is imperative. This study aimed to comprehensively characterize the expression of IC targets to inform drug development and design effective combinatorial strategies, to advance the search for optimized therapies for NSCLC. Methods: We analyzed the differential gene expression of IC targets in 537 primary lung adenocarcinoma (LUAD) samples and 59 normal lung tissue samples pre-immunotherapy receipt using RNA-sequencing data from The Cancer Genome Atlas. Gene expression of IC-targets including PDCD1 (PD-1), CD274 (PD-L1), CTLA4, TIGIT, LAG3, HAVCR2 (TIM-3), VSIR (VISTA), ICOS, CD276 (B7-H3), BTLA, IDO1, KLRD1 (CD94/NKG2A), NT5E (CD73), TNFRSF4 (OX-40), TNFRSF18 (GITR), and TNFRSF9 (4-1BB) were obtained. Differential gene expression was determined intra-tumorally by comparison of transcripts per million and inter-tumorally using the DESeq2 algorithm. Log2 fold change >0.5 and false discovery rate adjusted P<0.05 were used as criteria for significant differential expression. Hierarchical clustering was used to identify subsets of tumors with similar profiles of IC-targetable gene expression. Results: Tumors showed significantly increased expression of TNFRSF18 (GITR), NT5E (CD73), TNFRSF9 (4-1BB), LAG3, TIGIT, CTLA4, PD-1, BTLA, B7-H3, and OX-40 (Table 1). On the other hand, tumors exhibited significant downregulation of CD274 (PD-L1), HAVCR2 (TIM-3), ICOS, KLRD1 (CD94/NKG2A), and VSIR (VISTA). Hierarchical clustering revealed recurrent patterns of IC gene overexpression which were characterized by: 1) IDO1-hi, 2) CD276-mid + TNFRSF18-mid, 3) VSIR-hi, 4) CD276-hi, 5) NT5E-hi, and 6) CD276-mid + NT5E-mid. Interestingly, patterns of IC gene expression distinguish tumors from controls. Of note, high VSIR expression was specific to normal tissue rather than tumors. Conclusions: Our study identified many IC targetable genes that were significantly overexpressed in tumors. However, subsets of tumors showed distinct and segregable combinations of overexpressed IC genes. These results suggest heterogeneous mechanisms of immune evasion in NSCLC, which may explain suboptimal outcomes with anti-PD-1/PD-L1 based strategies in this patient population. Our findings emphasize the importance of biomarker-guided approaches for the optimal selection of ICs and the development of rational combinatorial immunotherapies in NSCLC.

PURPOSE: The COVID-19 pandemic led to unprecedented challenges in medical training, and we sought to assess the specific impact of COVID-19 on hematology-oncology (HO) fellowship programs. METHODS: We conducted a cross-sectional anonymous online survey of 103 HO program directors (PDs) in conjunction with the American Society of Hematology (ASH) and ASCO. We sought to assess the specific impact of COVID-19 on HO fellowship programs' clinical, educational, and research activities, evaluate perceptions regarding PD and trainee emotional and mental health, and identify ways to support programs. Data were analyzed using descriptive statistics, parametric and nonparametric tests, and multivariable logistic regression models. Responses to open-ended questions were analyzed with thematic analysis. RESULTS: Significant changes to fellowship activities included transitioning fellow training from outpatient clinics to telehealth (77.7%), shifting to virtual education (94.2%), and moving to remote research work (63.1%). A minority (21.4%) of PDs reported that their fellows were redeployed to cover non-HO services. Most PDs (54.4%) believed COVID-19 had a slight negative impact on fellowship training. PD self-reported burnout increased significantly from 15.5% prepandemic to 44.7% during the pandemic, and most PDs witnessed minor signs of fellow burnout (52.4%). Common PD concerns included inadequate supervision for telehealth activities, reduced opportunities for fellow advancement and promotion, lack of professional development activities, limited research operations and funding, program financial constraints, and virtual recruitment. CONCLUSION: We encourage institutions and national societies to allocate resources and develop programs that can support fellowships and mitigate the potential negative effects of COVID-19 on trainee and PD career development.

PURPOSE: Graduate medical and research training has drastically changed during the COVID-19 pandemic, with widespread implementation of virtual learning, redeployment from core rotations to the care of patients with COVID-19, and significant emotional and physical stressors. The specific experience of hematology-oncology (HO) fellows during the COVID-19 pandemic is not known. METHODS: We conducted a mixed-methods study using a survey of Likert-style and open-ended questions to assess the training experience and well-being of HO fellows, including both clinical and postdoctoral trainee members of the American Society of Hematology and ASCO. RESULTS: A total of 2,306 surveys were distributed by e-mail; 548 (23.8%) fellows completed the survey. Nearly 40% of fellows felt that they had not received adequate mental health support during the pandemic, and 22% reported new symptoms of burnout. Pre-existing burnout before the pandemic, COVID-19–related clinical work, and working in a primary research or nonclinical setting were associated with increased burnout on multivariable logistic regression. Qualitative thematic analysis of open-ended responses revealed significant concerns about employment after training completion, perceived variable quality of virtual education and board preparation, loss of clinical opportunities to prepare for independent clinical practice, inadequate grant funding opportunities in part because of shifting research priorities, variable productivity, and mental health or stress during the pandemic. CONCLUSION: HO fellows have been profoundly affected by the pandemic, and our data illustrate multiple avenues for fellowship programs and national organizations to support both clinical and postdoctoral trainees.

Introduction The COVID-19 pandemic has significantly affected many aspects of healthcare, including medical education and training. Its impact on hematology/oncology (HO) fellowship programs has not yet been characterized. Methods The American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO) sent an anonymous survey in June 2020 to all HO program directors (PDs) addressing program changes during the COVID-19 pandemic and their perception of impact on trainees' experience, education, and mental health. The survey included 32 multiple-choice and open-ended questions. Participants who completed the survey received a $10 gift card. Quantitative descriptive analyses of multiple-choice questions were conducted. Open-ended responses were analyzed qualitatively using NVivo software. Results Of 233 invited PDs, 103 (44%) respondents completed the survey; 22 additional surveys were incomplete and not included in the analysis. Table 1 summarizes PDs and program characteristics. In response to the pandemic, 42% (N=43) of programs removed fellows from outpatient clinics and 63% (N=65) changed research location to home (Figure 1). Most PDs reported their fellows were participating in telehealth for HO care (79%, N=81) and 21% (N=22) had their fellows re-deployed to cover medicine and other non-HO services. To support fellows' mental health most programs held additional virtual meetings (76%, N=78) and social events (52%, N=54). Twenty one percent of PDs (N=22) reported their program's professional development funds were completely cut or frozen and 17% (N=17) had funds cut slightly. Most PDs reported the pandemic negatively impacted fellowship overall (67% slight to significant negative impact, N=69), 72% identified clinical education as negatively impacted (72% slight to significant negative impact, N=74), and 35% (N=36) reported significant negative impact on research training/productivity. Twenty three percent (N=24) of PDs thought their fellows were not able to make good use of their time during the pandemic, professionally speaking. One third (33%, N=34) of PDs anticipated the pandemic would lead to lack of fellow clinical preparedness, 24% (N=25) with need to make up clinical rotations, and 15% (N=15) anticipated a negative impact on HO board pass rates. Post-pandemic, most PDs plan to maintain some virtual educational sessions (73%, N=75) and telehealth in fellows' continuity clinic (55%, N=57). Among PDs, the prevalence of burnout increased from 16% (N=16) pre-pandemic to 45% (N=46) during the pandemic (p&lt;0.0001). Seventeen percent (N=18) of PDs witnessed moderate signs of fellow burnout and 52% (N=54) witnessed minor signs of fellow burnout during the pandemic. Several educational and research constraints were identified via qualitative analysis: limited in-person clinical rotations, supervision of telehealth encounters, training year promotion and making up clinical time, limited professional development activities, board exam cancellations, and inability to perform research. Additional PD-identified trainee concerns included: ability to obtain childcare, separation from family, and Visa concerns among international fellows. PDs anticipated that financial constraints leading to cuts or removal of discretionary funds may have negative consequences for fellows' professional development activities and could force PDs to decrease program size in the future. PD recommendations for ASH and ASCO included: reducing or eliminating fellow membership fees, providing free access to educational materials and meetings, eliminating in-training examination fees, providing virtual sessions on career development, telehealth and wellness, virtual journal clubs, PD webinars focused on navigating fellowship issues and virtual interviews, and extending ASCO YIA funding for a second year. Conclusions PDs reported that their fellowship programs' clinical, educational, and research experiences have been impacted by the COVID-19 pandemic. PDs are concerned about the impact of budget cuts on fellows' professional and career development. PD burnout increased during the pandemic and most PDs observed at least mild burnout among their fellows. Professional societies can support fellowship programs by limiting fees and costs associated with membership, exams, and meetings, and increasing virtual opportunities for both fellows and PDs. Disclosures Velazquez Manana: Portola Pharmaceuticals: Other: Immediate family member stock ownership; Midatech: Other: Immediate family member stock ownership; Corbus Pharmaceuticals: Other: Immediate family member stock ownership.

Introduction: While the COVID-19 pandemic has affected many aspects of clinical care, research, and medical training, its impact on hematology-oncology trainees and professional development has not been described. The American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) sought to assess the impact of COVID-19 on fellows enrolled in hematology-oncology programs. Methods: In spring 2020, ASH and ASCO developed and administered a survey by e-mail to active hematology-oncology fellow members. Response formats used both a semi-Likert scale and open-ended text. Questions focused on fellow experiences and how changes in their programs have impacted their personal and professional lives across several domains. Multiple-choice responses were analyzed using descriptive statistics, and NVivo software was used for qualitative analysis of open-ended questions. Results: Respondent demographics are described in Table 1. Of 2,306 trainees, 620 (27%) responded to the survey. Most respondents continued patient care responsibilities during the pandemic (80%). Almost half of all trainees (47%) reported that they felt less productive than usual. Stress and/or anxiety about the current situation was the most cited factor affecting productivity in the overall cohort (Figure 1). One-third (33%) of respondents had volunteered or were assigned to clinical/non-clinical COVID-19-related efforts. Of the 90 visa holders in our cohort, 30% (N=27) reported experiencing issues with their visa/immigration status. Eight percent of respondents stated their career plans had changed due to COVID-19. Of those who said their plans had changed, 30 respondents were considering careers in academia pre-pandemic and 11 were considering private practice. However, only 14 respondents were considering academia post-pandemic while 19 were interested in private practice. Overall, most respondents had concerns about at least one of the following: salary reductions, availability of networking events, family well-being, mental health and obtaining a job (Figure 2). The prevalence of burnout increased from 22% (N=105) before the pandemic to 33% (N=161) during (p&lt;.001). Of the respondents who did not report burnout before COVID-19, 22% noted new-onset burnout during the pandemic. New-onset burnout prevalence varied based on the type of work respondents performed: no COVID-related work (17%), COVID-related non-clinical work (26%), and COVID-related clinical work (34%) (p&lt;0.01). The open-ended responses yielded several consistent themes. Clinical and educational constraints were enumerated: lost learning opportunities due to low patient volumes, unavailability of colleagues to discuss cases, and overall low perceived quality of virtual learning. Trainees also reported reduced motivation to complete work within a stipulated time frame due to lack of robust discussions in the virtual environment and technological challenges in navigating educational resources. Trainee research was also severely impacted as laboratories closed, experimental animal colonies were lost, and many research activities ceased. Respondents also expressed concern that cuts in research training initiatives and budgets would jeopardize faculty positions for graduating fellows and that funding for travel and conferences was suspended. Fellows' recommendations for ASH and ASCO included improved online education, virtual research training and networking opportunities, practical guidance on caring for immune-compromised patients during the pandemic, increased funding resources for trainees, mental health resources, and advocating on behalf of trainee visa holders. Conclusions: Hematology-oncology trainees reported their training experiences have been deeply impacted by the COVID-19 pandemic. A majority of trainees are concerned about the negative impact on career opportunities, research funding, financial well-being, and mental health. Burnout increased during COVID-19, especially in trainees who were assigned to specific COVID-related efforts. Training programs and professional societies can support trainees by increasing trainee research funding, online networking and learning opportunities, mental health resources and, support for international trainees. Disclosures Velazquez Manana: Corbus Pharmaceuticals: Other: Immediate family member stock ownership; Portola Pharmaceuticals: Other: Immediate family member stock ownership; Midatech: Other: Immediate family member stock ownership. Wun:Glycomimetics, Inc.: Consultancy.