Citations

Clinical trial participants do not reflect the racial and ethnic diversity of people with cancer. ASCO and the Association of Community Cancer Centers collaborated on a quality improvement study to enhance racial and ethnic equity, diversity, and inclusion (EDI) in cancer clinical trials. The groups conducted a pilot study to examine the feasibility, utility, and face validity of a two-part clinical trial site self-assessment to enable diverse types of research sites in the United States to (1) review internal data to assess racial and ethnic disparities in screening and enrollment and (2) review their policies, programs, procedures to identify opportunities and strategies to improve EDI. Overall, 81% of 62 participating sites were satisfied with the assessment; 82% identified opportunities for improvement; and 63% identified specific strategies and 74% thought the assessment had potential to help their site increase EDI. The assessment increased awareness about performance (82%) and helped identify specific strategies (63%) to increase EDI in trials. Although most sites (65%) were able to provide some data on the number of patients that consented, only two sites were able to provide all requested trial screening, offering, and enrollment data by race and ethnicity. Documenting and evaluating such data are critical steps toward improving EDI and are key to identifying and addressing disparities more broadly. ASCO and Association of Community Cancer Centers will partner with sites to better understand their processes and the feasibility of collecting screening, offering, and enrollment data in systematic and automated ways.

AbstractClinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p < .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.

Abstract Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in a cytokine storm that is associated with poor outcomes in patients. The activation of a NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome following SARS-CoV-2 infection has been shown to play a major role in inflammatory immune responses. In this study, we show that open reading frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro. The glycosylated ORF8 stimulates human CD14+/CD16+ monocytes to cause upregulation of proinflammatory cytokine production and cell surface marker expression within 24 hours. The data suggests that stimulation of human monocytes by ORF8 is not receptor mediated. Rather, ORF8 is likely phagocytosed by human monocytes. ORF8 then stimulates the monocytes by independently binding to the NACHT and LRR domains of the NLRP3 protein. Pharmacologic inhibition of NLRP3 significantly diminished the production of pro-inflammatory cytokines from ORF8-stimulated human monocytes. Finally, this study shows that the ORF8 protein is also secreted in patients with newly diagnosed coronavirus disease 2019 (COVID-19). Levels of ORF8 in the blood of patients diagnosed with COVID-19 correlated with disease mortality and trajectory of disease. ORF8 stimulation of monocytes causes pro-inflammatory cytokine production that leads to the development of severe COVID-19.

AbstractPlasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1–196), the 3‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3‐year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper‐CVAD or auto‐SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

Abstract The objective was to evaluate the impact of an interdisciplinary graduate level course on students’ knowledge and interests in immunotherapy and CAR-T cell therapy. It was a one week course conducted in November 2018. Students were surveyed before and after the course. The survey included questions regarding background, self-perceived knowledge/confidence in skills, and interests/predicted behaviors. Students were assigned to work in interdisciplinary teams to develop a research proposal. A total of 25 students taking the course for graduate level credit were surveyed. Of these, all 25 (100%) completed the surveys. Students came from variable backgrounds and were at different stages of graduate training. After completion of the course, there was a statistically significant increase in self-perceived knowledge of immunotherapy (mean±standard deviation score of 3.6±0.9 post-course vs 2.6±1.0 pre-course, on a 5 point Likert scale, P&lt;0.001), knowledge of the benchtop research to clinic translational process (3.7±0.8 post-course vs 3.0±0.9 pre-course, P&lt;0.001), confidence in critical reading skills (4.3±0.6 post-course vs 4.0±0.5 pre-course, P=0.008), confidence in immunotherapy focused grant writing skills (3.6±0.9 post-course vs 2.8±1.1 pre-course, P&lt;0.001), interest in working in interdisciplinary teams (4.8±0.4 post-course vs 4.6±0.6 pre-course, P=0.02), and interest in attending immunotherapy educational events (3.5±1.3 post-course vs 3.2±1.3 pre-course, P≤0.05). In conclusion, this course helps trainees to build knowledge and interest in the fields of immunotherapy and CAR-T cell therapy and can potentially serve as a platform for future educational courses in interdisciplinary, translational research.