Partnering with primary care to implement evidence based interventions (EBI) to address overdue colorectal cancer (CRC) screening in Connecticut (CT)

PURPOSE: Partnering with the largest Federally Qualified Health Center (FQHC) in New Haven, CT, the goal is to implement and test 4 evidence-based interventions (EBI) to increase CRC screening, while evaluating real-world implementation. Here, we report on the six-month (approximate) follow up of a cohort of 3,127 patients overdue for CRC screening who received 1 or more EBIs in October 2021. BACKGROUND: Sociocultural and medical concerns are barriers to colonoscopy uptake contributing to disparities in CRC screening. An additional barrier is system level capacity. COVID-19 associated delays exacerbated the existing backlog of individuals overdue for CRC screening, underscoring the need to expand Fecal Immunochemical Testing (FIT) capacity. This was particularly evident in the safety-net primary care setting that serves lower socio-economic status individuals living in urban New Haven, CT. METHOD(S): We are testing the unique and additive value of multiple evidence-based interventions (EBIs) for increasing CRC screening. The EBIs include the use of medical reminders, addressing the structural barriers (social determinants of health [SDOH]), and providing assistance from community health workers (CHW). We randomized 3,127 patients overdue for CRC screening to one of 4 arms of the study. All individuals received a reminder from their providers that they were due/overdue for CRC screening with instructions to contact the FQHC. Arm 2 also included information on SDOH barriers, Arm 3 included this same information with offer of navigation from CHW/navigator;and Arm 4 included the offer of CHW educational video and support if needed. Six-month (approximate) outcomes include: 1) Engagement with FQHC resulting in ordered test;2) completed test. Results by intervention will be assessed at 12 months. RESULT(S): Of the 3,127 randomized patients, ages 50-75, 77% were Hispanic (33%) or Black (44%). At 6+ months, a preliminary look at EMR data show that a minimum of 1,275 (40.8%) patients "engaged" with providers resulting in an ordered FIT Kit (n= 1174) or COMPLETED screening colonoscopy that was not associated with a positive FIT result (n = 102). 217 (18.5%) individuals completed the FIT testing with 13 requiring confirmatory colonoscopy (31% completed at this time). Thus, a minimum of 319 (10%) of 3,127 individuals in the cohort completed CRC screening at approximately 6 months post intervention. DISCUSSION: Despite investments in community engagement, stakeholder input, and FIT kit capacity building, the pandemic presented unforeseen challenges. Flexibility and steadfast commitment from FQHC providers and staff were critical to successful implementation during multiple waves of COVID-19, resulting in CRC screening ordered for 41% of cohort within 6 months of intervention. SUMMARY: At 6 months follow up of 3,127 individual who were overdue for CRC screening, one or more of 4 EBIs, in addition to system level efforts to address CRC screening, resulted CRC screening tests ordered for 41% of cohort with at least 10% completed screening.

Phase 1/2 Study of Agent-797, an Allogeneic Invariant Natural Killer T (Inkt) Cell Therapy, in Subjects with Moderate to Severe Acute Respiratory Distress Syndrome (Ards) Secondary to Sars-Cov-2 (Covid-19)

Background AgenT-797 is a novel allogeneic iNKT cell therapy demonstrating activity in malignances and serious viral infections (i.e., SARS-CoV-2). In response to inflammatory injury, iNKTs home to critical organs, including lungs, dampen proinflammatory cytokines and protect epithelial tissues. INKTs drive response through activation of innate and adaptive immunity, recruitment/trans-activation of NK, B, and T cells, and myeloid cells via contact and soluble mediators. iNKTs represent a novel and attractive potential immunotherapy for viral ARDS. This analysis presents results from an ongoing phase 1/2 study of agenT-797 in mechanically ventilated patients with moderate to severe ARDS secondary to COVID- 19;NCT04582201. Methods As of February 2022, patients on mechanical ventilation with confirmed moderate to severe (Berlin Definition) ARDS, secondary to COVID-19 were treated with a single infusion of agenT-797 at 100, 300, or 1000 x 106 iNKT cells. Primary endpoint was safety and secondarily, time to extubation, prevention of secondary infections, persistence and alloimmunity were evaluated. Clinical benefit was defined as improvement/resolution of viral ARDS evaluated as time to extubation and survival at 30 days post-infusion. Results Twenty evaluable patients were treated with agenT-797 with a median age of 66 years (range 26-77;85% >=65y). Patients enrolled early in pandemic (pre-vaccines) and were heavily pre-treated with remdesivir, steroids and/or tocilizumab. No dose-limiting toxicities were observed. Tolerability was favorable with no cytokine release syndrome (CRS), neurotoxicity, or severe immune-related AEs. One SAE was deemed possibly related to agenT-797 (Dyspnea, Grade 4). The most frequent AEs deemed possibly related was pyrexia (grade 1;n=6). Survival was 70% (14/20) in this predominantly elderly, mechanically ventilated population. Early signals of reduction in ARDS symptoms, rapid extubation, and reduction in secondary infections were observed. AgenT-797 was detected in peripheral blood up to day 6 post-infusion, consistent with a rapid translocation from blood to tissue. Spikes in the blood during D1 and D2 showed a dose-proportional relationship, however, increased dose did not lead to prolonged peripheral persistence. Additional translational and biomarker evaluation is underway. Conclusions In patients with severe viral ARDS secondary to SARS-COV-2, agenT-797 demonstrated encouraging survival and disease mitigating benefit with a favorable tolerability profile. The deep and broad activity observed is likely attributed to iNKT cells' ability to promote viral clearance, home to the lungs, and reduce inflammation. These findings support the potential for a variant-agnostic therapy for patients with viral ARDS, a condition for which there are currently no effective therapies.

Safety and Tolerability of SARS-Cov-2 Vaccination in Patients with Neuromuscular Disorders: A Single Center Experience

Objective: To describe side effects from SARS-Cov-2 vaccination and its effect on underlying neuromuscular disease amongst patients followed at the University of California, Irvine Neuromuscular Center. Background: Extensive data on safety and tolerability of SARS-Cov-2 vaccines exists for healthy individuals. However, patients with neuromuscular conditions and especially those on immune modulatory therapy were not included in the pivotal vaccine trials. It is primarily through expert consensus that vaccination is recommended for this patient population. Design/Methods: Patients were advised to inform the study team about their vaccination status. We collected data during in-person clinic visits or via telehealth encounters using a standardized questionnaire between December 2020 and August 2021. When information was provided about upcoming vaccination dates, patients were contacted within 2 weeks for follow up. Results: Information on 363 administered vaccine doses in 214 patients was recorded, including 199 Pfizer-BioNT, 155 Moderna and 9 Johnson & Johnson doses. Our cohort included 84 patients with myasthenia gravis (MG) and 34 with motor neuron disease (Amyotrophic Lateral Sclerosis, Primary Lateral Sclerosis). The remainder (96 patients) included other immunemediated disorders (idiopathic inflammatory myopathies, Chronic Inflammatory Demyelinating Neuropathy, Guillain-Barre Syndrome and other immune neuropathies) as well as acquired and inherited neuromuscular disorders (Inclusion Body Myositis, muscular dystrophy, inherited and acquired neuropathies). One patient with generalized MG had MG exacerbation, and another experienced impending crisis within one week of vaccine administration;both recovered with appropriate therapy. Detailed analyses of the dataset are being performed and will be presented at the meeting. Conclusions: SARS-Cov-2 vaccinations were well tolerated for the majority of our neuromuscular cohort, similar to what has been reported in healthy individuals. Vaccination did not result in disease exacerbation in the majority of patients with immune-mediated neuromuscular disorders.

Beyond Primary Care: Renewing the Community Health Center

United States community health centers address socioeconomic and environmental conditions and provide comprehensive primary care despite market forces that reinforce a medical model. Collaborating with 14 health center organizations, the RCHN Commu-nity Health Foundation promoted the original and broader health center vision of health, launching its population health management initiative in 2015. Although participating organizations were recognized as patient-centered medical homes and achieved rewards for quality, most identified gaps in their capacity for population health management. These challenges, addressed through peer learning and local initiatives, included engaging target populations, care coordination, socioeconomic and clinical data collection, and working with nontraditional local organizations. With relatively small funding, the zeal and enthusiasm for population health was revitalized among health center stall. The current pandemic and growing national concern for health disparities represents an opportunity to expand this broader vision of population health and to sustain it as the COVID-19 pandemic eventu-ally subsides.

Implementing evidence-based interventions (EBI) to increase uptake of fecal immunochemical test (FIT) colorectal cancer (CRC) screening in Vulnerable Populations

Purpose: We partnered with a local Federally Qualified Health Center (FQHC) to test implementation of evidence-based interventions (EBI) promoting Fecal Immunochemical Test (FIT) CRC screening in an environment in which colonoscopy has been the prevailing screening strategy. We report on implementation adaptations and preliminary results. Background: Sociocultural and medical concerns are barriers to colonoscopy uptake in some populations. An additional barrier to CRC screening is system level capacity for colonoscopy that results in a back log of cases and long wait times. With Covid-19, the additional backlog in overdue CRC screening has underscored the need to expand FIT testing capacity to address screening needs and to pre-empt further racial/ethnic and SES disparities in CRC outcomes. This trial tests the unique and additive value of multiple EBIs for increasing CRC screening (primarily through FIT testing, but also colonoscopy when indicated) while evaluating the success of implementing these approaches. EBIs include the use of medical reminders, addressing the structural barriers (social determinants of health [SDOH]), and assistance from community health workers. Methods: Participants (3500), ages 45-75, were identified from a large FQHC in New Haven, CT and determined to be overdue for CRC screening. Participants were randomly assigned to one of the four arms of the study: 1) Provider reminder (overdue for CRC screening) only;2) Provider Reminder + SDOH short message and one-size-fits all link to resources;3) Provider Reminder + SDOH short message and offer for individualized navigation (trained navigators from local community) to address SDOH and other barriers;4) Provider Reminder + offer to participate in a CRC educational program as phase 2 of the NCI's Screen to Save program (not an EBI). Preliminary data on uptake of CRC screening will be presented. Results: With input from stakeholders, we have: 1) lowered age eligibility from 50 to 45 to align with new guidelines;2) expanded the target population to 2 additional satellite clinics, more than doubling the proposed study enrollment;3) incorporated design changes in the patient reminders. The collaboration between research team and clinician stakeholders has been critical in minimizing disruptions to clinical workflow while assuring fidelity to the evidence-based interventions. Preliminary outcomes (within one month of intervention) on uptake of intervention across the 4 arms of the study, i.e., referral for CRC screening and test completion will be presented. Conclusion: The unique challenges of this urban community of primarily African American/Black, Hispanic/Latinx and/or low socioeconomic status individuals stem from the disproportionate burden of SDOH barriers. Findings will inform primary care setting implementation of EBIs to address the anticipated increase in disparities in CRC screening, exacerbated by COVID-19 changes in health care access and utilization, as well as the increased demand associated with the change in guidelines.

Impact of health navigation program on healthy lifestyle and cancer screening in population with significant social determinants of health (SDOH) barriers

Objective: Assess consumer experience and health impact among under-resourced individuals who were enrolled into longitudinal navigation to address social determinants of health (SDOH) needs and health goals related to cancer primary and secondary prevention. Background: The Yale Cancer Disparities Firewall Project is a multi-tiered initiative to address the social determinants of health (SDOH) and other challenges that prevent at-risk communities from receiving the full benefit of the many available cancer prevention and cancer screening options. A communityfacing health navigation program, staffed by community members who have received extensive multidisciplinary training is a central component of this program. Methods: Of the 61 currently enrolled individuals (all of whom are either African American/Black or Hispanic/Latinx), we collected questionnaire data from 24 individuals (39% response rate). In general, participants are enrolled for a minimum of 1 year, but most have been followed for 2 years. Respondents were similar to non-respondents with respect to race (60% were Black/African American vs 61.2%, respectively) and age (mean = 44.8 vs 47.2 years, respectively). Respondents were more likely to be female (85% vs 71.4%, p =.009), Hispanic/Latinx (35% vs 42%), but significantly less likely to be foreign-born (15% vs 26.5 %, p = .021). We assessed satisfaction with assigned navigator(s), uptake of referred services, knowledge gained, health behavior change, and self-rated health (SRH). Results: Per self-report, 79.2% of participants agreed and a further 12.5% somewhat agreed that they were overall satisfied with their experience with the health navigation program. Importantly, two-thirds (66.7%) agreed and a further 20.8% somewhat agreed that they changed their behavior to improve their health and well-being because of the program. Of the 5 health focused services offered, the most commonly reported uptake was physical activity (87.5%), followed by learning how to eat healthier and losing weight. Additionally, one third (33.3%) of participants received assistance with reducing or stopping smoking. In terms of secondary prevention, 62.5% of clients received assistance with cancer screening. Of the 5 SDOH focused services offered, the most common was assistance with finding food to eat (66.7%) followed by assistance with paying utilities (45.8%), a shift from the priority needs at baseline (40% needing food assistance, and 35% with housing concerns), presumably reflecting the additional strains associated with the COVID-19 pandemic. Conclusions: Against the backdrop of COVID-19, these findings suggest that addressing SDOH barriers through individual navigation is an important add-on service when facilitating access to services to maintain healthy lifestyle and adhere to cancer screening guidelines. Although this was a pilot program, we foresee the opportunity to utilize trained non-clinical navigators and/or community health workers and to promote cancer prevention in at risk communities.

First-Mind: Primary Analysis from a Phase Ib, Open-Label, Randomized Study to Assess Safety of Tafasitamab or Tafasitamab + Lenalidomide in Addition to R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

Introduction Tafasitamab is a humanized, Fc-modified, anti-CD19 monoclonal antibody (mAb) shown to enhance antibody-dependent cellular cytotoxicity and phagocytosis. It is approved by the FDA under accelerated approval (July 2020) in combination with lenalidomide (LEN) for treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in adult patients ineligible for autologous stem cell transplantation. To evaluate if newly diagnosed DLBCL patients would also benefit from this regimen, this Phase Ib study (First-MIND;NCT04134936) was designed to first assess the safety and tolerability of tafasitamab ± LEN in addition to rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in newly diagnosed DLBCL patients. Methods Eligible patients were ≥18 years old, with treatment-naïve DLBCL, international prognostic index (IPI) 2-5 and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients with known double- or triple-hit and transformed lymphoma were excluded. Patients were randomized 1:1 to either six 21-day [D] cycles of R-CHOP (R-CHO, D1;P, D1-5) + tafasitamab (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafasitamab + LEN (25 mg orally, D1-10) (Arm B). Granulocyte colony-stimulating factor and venous thromboembolism prophylaxis was mandatory. The primary safety endpoint was incidence of treatment-emergent adverse events (TEAEs);secondary endpoints included overall response rate (ORR), positron emission tomography (PET)-complete response (CR) rate, and partial response (PR) rate at end of treatment (EOT). Tumor measurements by PET/CT or PET/MRI at EOT were performed according to Lugano 2014 criteria within 6±2 weeks after Day 21 of the last treatment cycle the patient started. Results From December 2019 to August 2020, 83 patients were screened in nine countries across 34 sites in Europe and the US;66 were randomized (Arm A, n=33;Arm B, n=33). Data cut-off for this analysis: 13 March 2021. Median age was 64.5 years (range 20-86). Many patients had high-risk disease: IPI 2: 24/66 (36.4%), IPI 3: 29/66 (43.9%), IPI 4: 11/66 (16.7%), IPI 5: 2/66 (3.0%);ECOG PS ≥2: 6/66 (9.1%). Most patients had Stage III/IV disease 62/66 (93.9%);29/66 (43.9%) had bulky disease. All patients experienced at least one TEAE. The most frequent Grade ≥3 TEAEs by system organ class were blood and lymphatic disorders (81.8% patients overall), experienced by 24 patients (72.7%) in Arm A and 30 patients (90.9%) in Arm B. Grade ≥3 neutropenia and thrombocytopenia occurred in 19/33 (57.6%) and 4/33 (12.1%) (Arm A), and 28/33 (84.8%) and 12/33 (36.4%) (Arm B) patients, respectively;Grade ≥3 febrile neutropenia was experienced by 6/33 (18.2%) patients in each arm. Grade ≥3 infusion-related reactions to both rituximab and tafasitamab occurred in no patients in Arm A and one patient (3.0%) in Arm B, and 7/33 (21.2%) (Arm A) and 9/33 (27.3%) (Arm B) patients had a Grade ≥3 infection and/or infestation (Figure 1). Serious TEAEs occurred in 14/33 (42.4%) patients in Arm A and 17/33 (51.5%) patients in Arm B. Two out of 33 (6.1%) and one out of 33 (3.0%) patients discontinued study treatment due to TEAEs in Arms A and B, respectively. There were four deaths unrelated to tafasitamab and/or LEN (COVID-19 pneumonia, sepsis, and urosepsis). The average relative dose intensity of R-CHOP in each cycle was maintained in both arms. ORR at EOT was observed in 25/33 patients (75.8%;95% confidence interval [CI]: 57.7-88.9) in Arm A and 27/33 patients (81.8%;95% CI: 64.5-93.0) in Arm B. Conclusion These data suggest that both regimens are tolerable and do not impair dosing and scheduling of R-CHOP. Toxicities were similar to those expected with R-CHOP with or without LEN. With tumor follow-up still ongoing, the ORR at EOT suggests that patients with treatment-naïve DLBCL may achieve clinically meaningful efficacy tafasitamab and LEN in addition to standard treatment. A Phase III, multicenter, randomized, double-blind, placebo-controlled trial will assess efficacy and safety of R-CHOP + t fasitamab + LEN vs R-CHOP in newly diagnosed patients with high intermediate and high risk DLBCL, and is currently recruiting (frontMIND study;NCT04824092). Funding: MorphoSys AG. [Formula presented] Disclosures: Belada: Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding;Gilead Sciences: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding;Janssen-Cilag: Consultancy, Research Funding;Takeda: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding;MorphoSys AG: Consultancy, Research Funding;Debiopharm Group: Consultancy;Pharmacyclics: Research Funding;Archigen Biotech: Research Funding;Reddys: Research Funding. André: Johnson & Johnson: Research Funding;Roche: Other: Travel/accomodation/expenses, Research Funding;Incyte: Consultancy;Gilead: Consultancy, Other: Travel/Accommodations/Expenses;Karyopharm: Consultancy;Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses;Takeda: Consultancy, Research Funding;Celgene: Other: Travel/accomodation/expenses;AbbVie: Other: Travel/accomodation/expenses. Pérez Persona: Amgen: Consultancy, Other: Support for attending meetings and/or travel, Speakers Bureau;BMS/Celgene: Consultancy, Other: Support for attending meetings and/or travel, Speakers Bureau;AbbVie: Other: Support for attending meetings and/or travel, Speakers Bureau;Takeda: Speakers Bureau;Sanofi: Consultancy, Speakers Bureau;AstraZeneca: Speakers Bureau;GSK: Consultancy;Incyte: Consultancy. Staber: Roche: Consultancy, Honoraria, Research Funding;AbbVie: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Astra Zeneca: Consultancy, Honoraria;Takeda: Consultancy, Research Funding;MSD: Consultancy, Honoraria;BMS: Consultancy, Honoraria;Incyte: Consultancy, Honoraria, Research Funding;Beigene: Consultancy, Honoraria. Trneny: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Amgen: Consultancy, Honoraria;Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses;Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Celgene: Consultancy;1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Honoraria. Brackertz: MorphoSys AG: Current Employment. Shah: MorphoSys AG: Current Employment. Sporchia: MorphoSys AG: Current Employment. Burke: MorphoSys: Consultancy;Adaptive Biotechnologies: Consultancy;Verastem: Consultancy;AstraZeneca: Consultancy;Bristol Myers Squibb: Consultancy;Kymera: Consultancy;X4 Pharmaceuticals: Consultancy;AbbVie: Consultancy;SeaGen: Consultancy, Speakers Bureau;Kura: Consultancy;Roche/Genentech: Consultancy;Epizyme: Consultancy;Beigene: Consultancy, Speakers Bureau. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding;Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclon l antibody. In combination with lenalidomide (LEN), it received accelerated approval in July 2020 for adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), including arising from lowâ€'grade lymphoma, who are ineligible for autologous stem cell transplant (ASCT). Following FDA approval, we are now evaluating the safety and efficacy of tafasitamab in combination with LEN as an add-on to first-line therapy with R-CHOP in newly diagnosed patients with DLBCL.

Safety and Efficacy of Cusatuzumab in Combination with Venetoclax and Azacitidine (CVA) in Patients with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Eligible for Intensive Chemotherapy;An Open-Label, Multicenter, Phase 1b Study

Background: Acute myeloid leukemia (AML) is driven by aberrant leukemic stem cells (LSCs) that initiate and sustain malignancy. To circumvent resistance to therapy, combination therapies with additive mechanisms of action are needed. CD70, a tumor necrosis factor receptor ligand, and its receptor CD27 are expressed on LSCs and AML blasts, but not on hematopoietic stem cells. Cusatuzumab, a high-affinity humanized monoclonal anti-CD70 antibody, kills CD70-expressing cells by Fc domain-mediated effector functions and is a potent inhibitor of CD70-CD27 signaling. Here we report initial results of a study of cusatuzumab in combination with the current standard of care therapy, venetoclax plus azacitidine (CVA), in patients with untreated AML (de novo or secondary) ineligible for intensive chemotherapy due to age ≥75 years or medical comorbidities. Methods: The primary objective of this open label, multicenter, phase 1b study was to assess safety and tolerability of CVA. Key secondary objectives included response rate per ELN 2017 criteria and time to response. Patients received cusatuzumab 10 or 20 mg/kg IV on Day 3 and Day 17, a 3-day ramp-up of venetoclax (100, 200, and 400 mg PO) followed by 400 mg daily dosing, and azacitidine 75 mg/m 2 SC or IV on Days 1-7 of each 28-day cycle. Results: Based on data through Jul 9, 2021, 44 patients enrolled with median age 75 years (range 32-89), 36.4% had secondary AML, 40.9% had an ECOG performance status of 2, and ELN risk was favorable, intermediate and adverse in 18.2%, 20.5% and 61.4%, respectively. All patients received 20 mg/kg cusatuzumab except for 3 patients who received a starting dose of 10 mg/kg with the option to escalate to 20 mg/kg. Of these 3 patients, 1 escalated to 20 mg/kg. At a median follow-up of 29.1 weeks, the median number of treatment cycles was 4.0 (range 1.0-11.0). Grade 3 or above TEAEs were reported in 97.7% of patients;the most common (reported in ≥10%) were neutropenia (68.2%), thrombocytopenia (65.9%), febrile neutropenia (36.4%), anemia (34.1%), leukopenia (29.5%), sepsis (27.3%), and lymphopenia (15.9%). Treatment-emergent serious adverse events (SAEs) were reported in 75% of patients;the most common (reported in at least ≥5%) were febrile neutropenia (27.3%), sepsis (22.7%), COVID-19 (6.8%), and thrombocytopenia (6.8%). Treatment-emergent SAEs of grade ≥3 were reported in 72.7% of the patients. Infusion-related reactions (IRRs) were reported for 11.4% of patients with 2.3% at grade ≥3. Six (13.6%) patients discontinued treatment due to AEs, and 5 (11.4%) TEAEs resulted in death. The mortality rate within 30 days from start of treatment was 4.5%. Table 1 summarizes best response to study treatment. In the intent-to-treat analysis set (n=44) complete remission (CR) rate was 45.5%, while CR + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi) was 77.3%;MLFS was observed in 11.4% of patients. Of 34 responders (defined as CR, CRi or CRh), 47% were MRD negative by flow cytometry at or after achievement of response. Median time to first response for patients who achieved CR, CRh or CRi was 4.21 (3.0-25.0) weeks. Best response rates in the post-hoc response evaluable analysis set (n=42) that excluded two patients who died before the first disease evaluation were: CR in 47.6%, CR + CRh + CRi in 81.0% and MLFS in 11.9% of patients (Table 1). The majority (97.1%) of responders experienced at least one cycle delay in administration of CVA post response. Conclusions: Cusatuzumab administered in combination with venetoclax and azacitidine to elderly patients with untreated AML was generally well tolerated and demonstrated a safety profile consistent with that previously reported with venetoclax-azacitidine, with the addition of generally manageable IRRs. Response rates support an additive effect of cusatuzumab to the standard of care with potential for improved clinical outcomes. However, further clinical trials are needed for validation of these initial results. HK and GB contributed equally to this publ cation. [Formula presented] Disclosures: Roboz: AstraZeneca: Consultancy;Janssen: Research Funding;Bristol Myers Squibb: Consultancy;Jasper Therapeutics: Consultancy;Agios: Consultancy;Novartis: Consultancy;Amgen: Consultancy;Blueprint Medicines: Consultancy;Janssen: Consultancy;Helsinn: Consultancy;Daiichi Sankyo: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Mesoblast: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Astex: Consultancy;Bayer: Consultancy;Astellas: Consultancy;Roche/Genentech: Consultancy;Pfizer: Consultancy;Otsuka: Consultancy. Aribi: Seagen: Consultancy. Brandwein: Astellas: Honoraria;Jazz: Honoraria;Amgen: Honoraria;Taiho: Honoraria;BMS/Celgene: Honoraria;Pfizer: Honoraria;Abbvie: Honoraria;University of Alberta: Current Employment. Döhner: Astellas: Consultancy, Honoraria, Research Funding;AstraZeneca: Consultancy, Honoraria;Berlin-Chemie: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria, Research Funding;Agios: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;GEMoaB: Consultancy, Honoraria;Helsinn: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Jazz: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Oxford Biomedicals: Consultancy, Honoraria;Pfizer: Research Funding;Roche: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding;Astex: Consultancy, Honoraria;Ulm University Hospital: Current Employment. Fiedler: Jazz Pharmaceuticals: Consultancy, Other: support for meeting attendance;Abbvie: Consultancy, Honoraria;Morphosys: Consultancy;Celgene: Consultancy;Pfizer: Consultancy, Research Funding;Novartis: Consultancy;ARIAD/Incyte: Consultancy;Amgen: Consultancy, Other: support for meeting attendance, Patents & Royalties, Research Funding;Servier: Consultancy, Other: support for meeting attendance;Daiichi Sankyo: Consultancy, Other: support for meeting attendance;Stemline: Consultancy. Gandini: argenx: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Geddes: University of Calgary: Current Employment;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy;Paladin: Consultancy;Janssen: Research Funding;Geron: Research Funding;Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hou: University of Pittsburgh Medical Center Hillman Cancer Centers: Current Employment;AbbVie: Honoraria;AstraZeneca: Honoraria;Karyopharm: Honoraria;Chinese American Hematology Oncology Network: Membership on an entity's Board of Directors or advisory committees. Howes: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Hultberg: argenx: Current Employment, Patents & Royalties. Huselton: University of Rochester: Current Employment. Jacobs: Argenx BV: Current Employment, Current equity holder in publicly-traded company;University of Antwerp: Ended employment in the past 24 months. Kane: Janssen R&D, part of Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Lech-Marańda: Takeda: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors r advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Louwers: argenx: Current Employment, Patents & Royalties: Patents (no royalties). Nottage: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Platzbecker: Novartis: Honoraria;AbbVie: Honoraria;Janssen: Honoraria;Celgene/BMS: Honoraria;Geron: Honoraria;Takeda: Honoraria. Rampal: Pharmaessentia: Consultancy;BMS/Celgene: Consultancy;Abbvie: Consultancy;Sierra Oncology: Consultancy;Incyte: Consultancy, Research Funding;Blueprint: Consultancy;Disc Medicine: Consultancy;Jazz Pharmaceuticals: Consultancy;Constellation: Research Funding;Kartos: Consultancy;Stemline: Consultancy, Research Funding;CTI: Consultancy;Novartis: Consultancy;Memorial Sloan Kettering: Current Employment. Salman: Janssen: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Shah: Janssen R&D, part of Johnson & Johnson: Current Employment. Stuart: Clinical Drug Development Consultants LLC: Current Employment;Argenx: Consultancy;Cleave Therapeutics: Consultancy;Triphase Accelerator Corp: Consultancy;IgM Biosciences: Consultancy;Revolution Medicines: Consultancy;Jiya Corp:Consultancy;Geron Corp: Current holder of individual stocks in a privately-held company. Subklewe: Janssen: Consultancy;Pfizer: Consultancy, Speakers Bureau;Takeda: Speakers Bureau;Klinikum der Universität München: Current Employment;MorphoSys: Research Funding;Novartis: Consultancy, Research Funding, Speakers Bureau;Roche: Research Funding;Seattle Genetics: Consultancy, Research Funding;Miltenyi: Research Funding;Gilead: Consultancy, Research Funding, Speakers Bureau;Amgen: Consultancy, Research Funding, Speakers Bureau;BMS/Celgene: Consultancy, Research Funding, Speakers Bureau. Sumbul: argenx: Current Employment. Wang: Takeda: Consultancy, Honoraria, Other: Advisory board;Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board;Genentech: Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Consultancy, Speakers Bureau;Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau;Novartis: Consultancy, Honoraria, Other: Advisory Board;Mana Therapeutics: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau;Rafael Pharmaceuticals: Other: Data safety monitoring committee;Gilead: Consultancy, Honoraria, Other: Advisory board;Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board;PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board;Genentech: Consultancy;MacroGenics: Consultancy. Wierzbowska: Jazz: Research Funding;Pfizer: Honoraria;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Astellas: Honoraria, Membership on an entity's Board of Directors or advisory comm ttees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS: Honoraria. Yao: Statagize LLC: Current Employment;Puma Biotechnology, Inc.: Ended employment in the past 24 months;Argenx: Consultancy. Yee: Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen: Research Funding;TaiHo: Membership on an entity's Board of Directors or advisory committees;Otsuka: Membership on an entity's Board of Directors or advisory committees;Onconova: Research Funding;Pfizer: Membership on an entity's Board of Directors or advisory committees;Tolero: Research Funding;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Paladin: Membership on an entity's Board of Directors or advisory committees;MedImmune: Research Funding;AbbVie: Honoraria;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Forma Therapeutics: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;Geron: Research Funding;Genentech: Research Funding;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Jazz: Research Funding. Kantarjian: Immunogen: Research Funding;Astra Zeneca: Honoraria;KAHR Medical Ltd: Honoraria;Astellas Health: Honoraria;Pfizer: Honoraria, Research Funding;NOVA Research: Honoraria;Ascentage: Research Funding;Precision Biosciences: Honoraria;Novartis: Honoraria, Research Funding;Aptitude Health: Honoraria;Ipsen Pharmaceuticals: Honoraria;Jazz: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Amgen: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;Taiho Pharmaceutical Canada: Honoraria. Borthakur: Protagonist: Consultancy;Ryvu: Research Funding;Astex: Research Funding;GSK: Consultancy;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;University of Texas MD Anderson Cancer Center: Current Employment;ArgenX: Membership on an entity's Board of Directors or advisory committees.

Doctoral supervision and COVID-19: Autoethnographies from four faculty across three continents

Doctoral students represent the fresh and creative intellectuals needed to address the many social, economic, political, health care, and education disparities that have been highlighted by the 2020 pandemic. Our work as doctoral student supervisors could not be more central nor vital than it was at the beginning of, during, and following the pandemic. Written during the pandemic of 2020, the purpose of this paper was to describe how four faculty from three continents navigated their relationships with doctoral students in the research and dissertation phase of their doctoral programs. Using a common set of prompts, four faculty members each wrote an autoethnography of our experience as doctoral student supervisors. Even though our basic advising philosophies and contexts were quite different, we learned about the possibility and power of resilience, empathy, and mentoring online. Our findings imply that new online practices could be closely examined and retained after the pandemic to expand the reach, depth and impact of doctoral education.

Diagnosing COVID-19; towards a feasible COVID-19 rule-out protocol.

INTRODUCTION: We present the results of the COVID-19 rule-out protocol at Ghent University Hospital, a step-wise testing approach which included repeat NFS SARS-CoV-2 rRT-PCR, respiratory multiplex RT-PCR, low-dose chest CT and bronchoscopy with BAL to confirm or rule-out SARS-CoV-2 infection in patients admitted with symptoms suggestive of COVID-19. RESULTS: Between 19 March 2020 and 30 April 2020, 455 non-critically ill patients with symptoms suspect for COVID-19 were admitted. The initial NFS for SARS-CoV-2 rRT-PCR yielded 66.9%, the second NFS 25.4% and bronchoscopy with BAL 5.9% of total COVID-19 diagnoses. In the BAL fluid, other respiratory pathogens were detected in 65% (13/20) of the COVID-19 negative patients and only in 1/7 COVID-19 positive patients. Retrospective antibody testing at the time around BAL sampling showed a positive IgA or IgG in 42.9 % of the COVID-19 positive and 10.5% of the COVID-19 negative group. Follow-up serology showed 100% COVID-19 positivity in the COVID-19 positive group and 100% IgG negativity in the COVID-19 negative group. CONCLUSION: In our experience, bronchoscopy with BAL can have an added value to rule-in or rule-out COVID-19 in patients with clinical and radiographical high-likelihood of COVID-19 and repeated negative NFS testing. Furthermore, culture and respiratory multiplex PCR on BAL fluid can aid to identify alternative microbial etiological agents in this group. Retrospective analysis of antibody development in this selected group of patients suggests that the implementation of serological assays in the routine testing protocol will decrease the need for invasive procedures like bronchoscopy.