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OBJECTIVE Despite advancement of thrombectomy technologies for large-vessel occlusion (LVO) stroke and increased user experience, complete recanalization rates linger around 50%, and one-third of patients who have undergone successful recanalization still experience poor neurological outcomes. To enhance the understanding of the biomechanics and failure modes, the authors conducted an experimental analysis of the interaction of emboli/artery/devices in the first human brain test platform for LVO stroke described to date. METHODS In 12 fresh human brains, 105 LVOs were recreated by embolizing engineered emboli analogs and recanalization was attempted using aspiration catheters and/or stent retrievers. The complex mechanical interaction between diverse emboli (elastic, stiff, and fragment prone), arteries (anterior and posterior circulation), and thrombectomy devices were observed, analyzed, and categorized. The authors systematically evaluated the recanalization process through failure modes and effects analysis, and they identified where and how thrombectomy devices fail and the impact of device failure. RESULTS The first-pass effect (34%), successful (71%), and complete (60%) recanalization rates in this model were consistent with those in the literature. Failure mode analysis of 184 passes with thrombectomy devices revealed the following. 1) Devices loaded the emboli with tensile forces leading to elongation and intravascular fragmentation. 2) In the presence of anterograde flow, small fragments embolize to the microcirculation and large fragments result in recurrent vessel occlusion. 3) Multiple passes are required due to recurrent (15%) and residual (73%) occlusions, or both (12%). 4) Residual emboli remained in small branching and perforating arteries in cases of alleged complete recanalization (28%). 5) Vacuum caused arterial collapse at physiological pressures (27%). 6) Device withdrawal caused arterial traction (41%), and severe traction provoked avulsion of perforating and small branching arteries. CONCLUSIONS Biomechanically superior thrombectomy technologies should prevent unrestrained tensional load on emboli, minimize intraluminal embolus fragmentation and release, improve device/embolus integration, recanalize small branching and perforating arteries, prevent arterial collapse, and minimize traction.

11014 Background: The well-being of oncology providers (OP) is in jeopardy with increasing workload, limited resources, and personal challenges that result from the COVID-19 pandemic. We aim to evaluate the impact of COVID-19 on work-related (WR) satisfaction and fatigue among OP in Latin America. Methods: We conducted an international cross-sectional online survey of OP practicing in Latin America. The survey was administered in English, Spanish, and Portuguese. Data was analyzed using descriptive statistics and Chi-square tests. Results: In August 2020, 704 OP from 20 Latin American countries completed the survey (77% of 913 who started the survey). Table outlines baseline characteristics. Higher frequency of WR fatigue (67% vs. 58%, p=0.010) and exhaustion (81% vs. 70%, p=0.001) were reported by OP who cared for patients with COVID-19, compared to OP who cared for patients without COVID-19. Providers that observed delays in referrals to radiation (p=0.002) and surgery (p=0.04) reported WR fatigue at higher rates than their counterparts. Higher exhaustion (p=0.016) and dissatisfaction (p=0.046) were reported by OP who lacked access to supportive services, as social work. A significantly higher proportion of women reported WR fatigue (72% vs. 56%, p=0.003) and exhaustion (86% vs. 68%, p=0.001), when compared to men. Women were more likely than men to endorse higher current levels of fatigue when compared to pre-COVID-19 (61% vs. 46%, p=0.0001). To reduce stress, women were more likely than men to cut the time spent watching the news (p=0.002). Both genders declined research collaborations and speaking opportunities. Conclusions: Fatigue and dissatisfaction with work-life were prevalent among OP in Latin America. Higher rates of WR fatigue were seen in women, OP caring for patients with COVID-19, and OP with patients who experienced cancer care delays. Our data imply that OP may be a prime target for psychosocial support, particularly as current challenges will continue for the foreseen future. Baseline characteristics (N=704).[Table: see text]

9089 Background: RET fusions are targetable oncogenic drivers in 1–2% of non-small cell lung cancer (NSCLC). ARROW (NCT03037385) supported the US FDA approval of pralsetinib, a highly potent oral selective RET inhibitor for RET-altered NSCLC and thyroid cancer. Here, we present updated results for a larger population of patients with RET fusion–positive NSCLC enrolled in ARROW. Methods: ARROW is a phase 1/2 open-label study conducted at 84 sites in 13 countries. Phase 2 expansion cohorts included patients with RET fusion–positive NSCLC. Initially, all treatment-naïve patients were not candidates for platinum-based therapy, a requirement removed by protocol amendment in July 2019. Primary objectives are overall response rate (ORR; blinded independent central review [BICR] per RECIST v1.1), assessed for patients with baseline measurable disease, and safety. Results: Updated analyses were completed as of Nov 6, 2020 (data cut-off), for patients who initiated pralsetinib 400 mg QD by May 22, 2020 (enrollment cut-off). Efficacy results, including analyses for treatment-naïve patients enrolled after eligibility criteria were revised to allow candidates for platinum-based therapy, are shown in the Table. Conclusions: Pralsetinib showed rapid, potent, and durable clinical activity in patients with RET fusion-positive NSCLC (regardless of prior therapies), including poor prognosis patients not eligible for platinum-based therapy. Overall, pralsetinib was well-tolerated. These data highlight the need for RET testing early in the course of disease to identify candidates who may benefit from treatment with pralsetinib. Clinical trial information: NCT03037385. [Table: see text]

e19547 Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities, and is associated with an inferior prognosis compared to other primary cutaneous B-cell lymphomas. Immunochemotherapy with or without involved-field radiation therapy (IFRT) is considered standard, front-line therapy. Interestingly, over-expression of PD-L1/PD-L2 has been shown in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. Therefore, we describe the outcomes of 1) immunochemotherapy with and without IFRT as front-line treatment of PCDLBCL, LT, and 2) ICIs in the relapsed/refractory setting. Methods: We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from January 1, 2000 to December 31, 2020. Using the Kaplan-Meier method, we calculated progression-free survival (PFS), duration of response (DOR), and overall survival (OS) in patients who received front-line R-CHOP with and without IFRT, and salvage ICI therapy for relapsed/refractory disease. Results: A total of 28 patients with PCDLBCL, LT were identified. The median age at diagnosis was 71.6 years (range 48.0-91.7), 50% (N = 14) were male, and 78.6% (N = 22) had disease involvement of the lower extremities at diagnosis. For front-line treatment, 31.2% (N = 9) received R-CHOP with IFRT, and 31.2% (N = 9) received R-CHOP without IFRT. The median PFS in patients treated with R-CHOP plus IFRT was 41.8 months [95% CI: 30.2-69.6] compared to 13.7 months [95% CI: 10.7-27.7; p= 0.01] in those treated with R-CHOP without IFRT. The median OS in patients treated with R-CHOP plus IFRT was 74.7 months [95% CI: 53.0-108.6] compared to 38.2 months [95% CI: 26.0-80.4; p= 0.14] in those treated with R-CHOP without IFRT. Patient and disease characteristics were similar among these two groups. ICIs were used in 17.9% (N = 5) of patients with relapsed/refractory, PCDLBCL, LT, and these patients had received a median of three (range 2-10) prior systemic therapies. The overall response rate was 60% as three patients treated with ICIs achieved a complete response, and the other two patients showed no clinical response. The median DOR from ICIs was 23.0 months [95% CI: 3.6-26.0]. The median PFS from ICI therapy was 10.2 months [95% CI: 3.6 – not reached]. Only one of the five patients was noted to have a mild side effect from ICI treatment (elevated alkaline phosphatase, grade 1). Conclusions: R-CHOP with IFRT was associated with a longer median PFS compared to R-CHOP without IFRT as front-line therapy for PCDLBCL, LT. Furthermore, ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients and a favorable safety profile were observed in this study. Further studies would be of benefit to confirm our findings.

e19501 Background: The current standard of care for patients with relapsed or refractory (RR) diffuse large B-cell lymphoma (DLBCL) following frontline immunochemotherapy (IC) is salvage therapy, followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) rescue in patients responding to salvage therapy. Time to first relapse (or refractory status) and response to salvage therapy in patients with RR DLBCL may reflect the chemosensitivity of the underlying disease. The aim of this study is to determine whether these factors impact post-ASCT outcomes. Methods: Patients with DLBCL that relapsed after R-CHOP or R-CHOP-like frontline therapy who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma and transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using Kaplan-Meier method and Cox proportional hazards models. Results: A total of 437 patients with RR DLBCL who underwent salvage therapy and ASCT were identified. 280 (64%) were male. Median time from initial diagnosis to 1st relapse/salvage was 1.0 years (range 0.1-16.4). A median of 1 line (range 1-3) of salvage therapy was required. Response prior to ASCT was complete response (CR) in 211 (48%), partial response in 199 (46%), stable disease in 24 (5%), and unknown in 3 (1%) patients. Median age at ASCT was 61 years (range 19-78), and median follow up after ASCT was 8.0 years (95% CI 7.2-8.7). Median PFS and OS was 2.7 (95% CI 1.5-4.3) and 5.4 (4.2-7.4) years, respectively. Time to 1st relapse/salvage (≤1 vs 1-2 vs > 2 years) was not associated with PFS (median 0.8 vs 2.4 vs 4.9 years, p = 0.170) but was associated with OS (2.4 vs 7.4 vs 6.8 years, p = 0.013). Patients who required > 1 line of salvage therapy had significantly inferior PFS (median 0.3 vs 4.5 years, p < 0.001) and OS (0.9 vs 7.4 years, p < 0.001). In addition, patients who failed to achieve a CR prior to ASCT had significantly worse PFS (median 0.8 vs 5.3 years, p < 0.001) and OS (2.7 vs 9.2 years, p < 0.001). In multivariate Cox regression models adjusted for age and sex, time to 1st relapse/salvage was not associated with PFS (p = 0.313) or OS (p = 0.081); however, lines of salvage and response prior to ASCT remain significantly prognostic for PFS ( > 1 line of salvage: HR 2.14, 95% CI 1.59-2.87, p < 0.001; non-CR: HR 1.61, 95% CI 1.26-2.05, p < 0.001) and OS ( > 1 line of salvage: HR 2.25, 95% CI 1.66-3.05, p < 0.001; non-CR: HR 1.63, 95% CI 1.26-2.12, p < 0.001). Conclusions: In patients with RR DLBCL following frontline IC, requiring more than 1 line of salvage therapy and failure to achieve CR are strong independent risk factors for poor PFS and OS after ASCT. Novel therapies such as CAR-T cell therapy should be studied in this population.

7558 Background: A low absolute lymphocyte to monocyte ratio (ALC/AMC) has been found to predict decreased survival in lymphoma patients receiving chemotherapy and stem cell transplant. We report its clinical significance and additional cellular phenotype changes in patients receiving chimeric antigen receptor T-cell (CART) therapy. Methods: Records were reviewed for patients (pts) who received axicabtagene ciloleucel between 6/2016 and 12/2020. Receiver operator curve was generated using nominal logistic regression to predict CR as best response. Survivals were calculated using Kaplan- Meier method. Blood immune phenotype were assayed by multiparametric flow. Principle component analysis (PCA) was performed using ClusterVis. Results: Low ALC/AMC (≤0.8) prior to lymphodepletion (LD) chemotherapy on day -5 was associated with lower CR rate (AUC=0.68, Table). Our cohort of 81 pts had similar baseline characteristics except that noted in Table. Low ALC/AMC ratio is associated with shorter EFS and OS (EFS: 2.6 vs. 6.4 months, P<0.0001; OS: 5.3 months vs. not reached, P=0.0006), respectively. Prognostic association remained significant in multivariate analysis including ASCT, bridging therapy and CRP. Interestingly, compared to the high ALC/AMC group, the low ALC/AMC group had decreased CD8 Tem, increased CD16+CCR2+ monocytes and increased monocytes’ producing IL12, IL-10, and IL-1β (n=26). Unsupervised PCA identified 3 clusters: 1. Low ALC/AMC, all non-CR; 2. High ALC/AMC, some non-CR; 3. High ALC/AMC, all CR. Compared to cluster 1 and 2, cluster 3 had increased CD4 Tnaive, CD8 Tcm and IL-17 producing CD4 T and NK cells. Conclusions: ALC/AMC is a clinically accessible test that is strongly associated with CAR-T response and survival. Immune characterization revealed that the biologic effect is not just associated with cell ratio. Increased inflammation has been found to negatively impact CAR-T response, with some cytokines known to be from the myeloid lineage. We show that CRP is elevated in the low ALC/AMC group with increased cytokine production by monocytes. In addition, presence of T cell subset and IL-17 producing cells, before LD, are associated with clinical response. Further investigation on optimizing host immunity may help improve clinical outcome with CAR-T.[Table: see text]

7542 Background: 60-70% of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) can be cured with R-CHOP or R-CHOP-like immunochemotherapy. However, patients ≥80 years of age were either excluded or underrepresented in modern DLBCL trials, and their outcomes are understudied. The aim of this study is to define the survival trends and risk factors for inferior survival in older adult patients with DLBCL. Methods: Patients with newly diagnosed DLBCL were identified from the National Cancer Database (2004-2017, representing the rituximab era). Clinical characteristics, treatment, and outcomes were compared between patients ages ≥ 80, 65-79, and < 65 years. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: A total of 231,756 patients with newly diagnosed DLBCL were identified; 46,250 (20%) were ≥80 years, 87,702 (38%) were 65-79 years, and 97,904 (42%) were < 65 years. Patients ≥80 years were more likely to have a higher Charlson-Deyo Comorbidity Index score (CDS) (CDS ≥2, 12% vs 11% vs 8%, p = 0.001), less likely to receive systemic chemotherapy (63% vs 83% vs 89%, p < 0.001), and more likely to receive treatment at a non-academic center (71% vs 65% vs 48%, p < 0.001), compared to patients 65-79 and < 65 years, respectively. Median overall survival (OS) was significantly worse for patients ≥80 years compared to patients 65-79 years (11.6 vs 61.0 months, p = 0.001) and patients < 65 years (11.6 vs 178.1 months, p = 0.001). During the study period, the median OS had only minimally improved for patients ≥80 years (10.6 months in 2004-2007 vs 11.5 months in 2008-2011 vs 12.3 months in 2012-2016, p = 0.006). In contrast, the OS improvement appears more meaningful in patients 65-79 years (median in months: 51 vs 61.2 vs 65.9, p = < 0.001) and patients < 65 years (median in years: 14.6 vs 11.3 vs not reached, p < 0.001) in the prespecified intervals (2004-07, 2008-11, and 2012-16). In multivariate analysis, the most substantial risk factor for worse survival in patients ≥80 years was not receiving systemic therapy (hazard ratio [HR] = 3.26, 95%CI = 3.01-3.54, p = 0.001). Other risk factors associated with worse survival included high-risk IPI score (HR = 2.16, 95%CI = 1.96-2.39, p = 0.001), CDS score ≥2 (HR = 1.56, 95%CI = 1.40-1.73, p = 0.001), male sex (HR = 1.16, 95%CI = 1.09-1.24, p = 0.001), B symptoms at diagnosis (HR = 1.16, 95%CI = 1.08-1.25, p = 0.001), and treatment at a non-academic center (HR = 1.1, 95%CI = 1.01-1.20, p = 0.001). Conclusions: Patients ≥ 80 years of age with DLBCL have a significantly inferior survival which has not meaningfully improved in recent years. More than 1/3 of patients ≥ 80 years did not receive systemic therapy. Older adult patients with DLBCL should be assessed for fitness for chemotherapy using validated geriatric assessment tools. Novel therapeutic strategies with favorable safety profiles are urgently needed for this expanding patient population.

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p<0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p<0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p<0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p<0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

7522 Background: Patients with newly diagnoseddiffuse large B-cell lymphoma (DLBCL) who achieve event-free survival at 24 months (EFS24) following immunochemotherapy (IC) have excellent overall survival (OS) similar to that of age- and sex-matched general population. The standard of care for patients with relapsed or refractory (RR) DLBCL following frontline IC is salvage therapy followed by autologous stem cell transplant (ASCT). The goal of this study is to evaluate the role of progression-free survival (PFS) at 24 months (PFS24) as a landmark after ASCT in patients with RR DLBCL. Methods: Patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Post-ASCT PFS, OS, and post-relapse survival (PRS) were plotted by Kaplan-Meier method, and cumulative incidences of relapse vs non-relapse mortality (NRM) and different causes of death were compared accounting for competing events. Statistical analyses were performed in EZR v1.54. Results: A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow up of 8.0 years (95% CI 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, post-ASCT relapse rate was much higher than NRM rate (48.1 vs 9.1% at 5-year). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and NRM were similar (14.8% and 12.3% at 5-year). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma related and unrelated death rates were similar after achieving PFS24 (Table). For all patients who had a post-ASCT relapse, median PRS was 0.7 years (95% CI 0.5-0.9), and late relapse ( > 2 vs ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] vs 0.5 [0.3-0.7] years, p < 0.001). Conclusions: Post-ASCT PFS24 is an important prognostic predictor of post-ASCT outcomes in patients with RR DLBCL following frontline IC.[Table: see text]

e18521 Background: About 40% of the US population are from minority groups. Minority pts are under-represented in oncology clinical trials, which limits the applicability of results to the general population and perpetuates poor relationships between healthcare systems and minority communities. This assessment investigated underlying causes of this lack of minority representation in clinical trials and proposes plans to promote diversity. Methods: To better understand the limited inclusion of under-represented pts in oncology clinical trials, 10 specialists in cancer care were selected to provide their perspectives. Specialists were chosen because of their experience enrolling minority pts in clinical trials and met virtually in Dec 2020 via Within3, a secure digital communication platform, to discuss obstacles faced in recruiting minority pts and potential strategies to address these concerns. Specificity and alignment in responses were achieved through software analytics and follow-up queries. Results: The 10 specialists identified as Asian (10%), Black (30%), White (50%), and Hispanic (10%), and began practicing medicine in the 1980s-2010s. All are involved in clinical research and treat a range of minority pts in both urban and suburban settings. Most specialists (8/10) reported treating > 20 minority pts with cancer annually. However, few specialists (2/10) reported that > 20% of their minority pts have enrolled in clinical trials. Specialists agreed that minority pts experience barriers to participation in clinical research, including lack of trust in the healthcare system, materials in their native languages, financial support, minority investigators involved in clinical trials, and accessible study sites. The specialists proposed strategies that could be implemented to increase minority enrollment. These included study sites where minority populations live and industry funded outreach and educational efforts in minority communities. If sites are more accessible, this can reduce time and financial pressures associated with study participation. The specialists recommended that studies be designed to be more supportive of minority populations, specifically regarding inclusion and exclusion criteria and reimbursement of costs. They also advised that increased diversity among clinical researchers and allied personnel may increase the ability of the clinical team to connect with pts and assist in building trust in their communities. Finally, they emphasized the importance of providing informed consent forms and study materials in pts’ native languages. Conclusions: While challenges exist to increasing diversity in oncology clinical studies, a broad consortium of clinical specialists agreed that they can be addressed by community outreach and education, making study sites more accessible, availability of study materials in pts’ native languages, and improving diversity of clinical teams.