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e16200 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme expressed by HCC which helps to orchestrate immune suppression within the tumor microenvironment (TME) and may contribute to primary and acquired resistance of PD-(L)1 inhibitors. BMS-986205 is a novel oral drug that potently and selectively inhibits IDO1. This Phase I/II study is evaluating the safety and tolerability of the combination of BMS-986205 and nivolumab as first-line therapy in HCC. Methods: Patients (pts) ≥18y with untreated, unresectable/metastatic HCC received BMS-986205 in combination with nivolumab. A fixed dose of Nivolumab 240mg/m2 IV was administered on Day 1 of each 14-day cycle. BMS-986205 was an oral tablet administered daily; a total of two dose levels (50-100mg) were given to determine dose limiting toxicities (DLT) during the dose-escalation Phase I of the study. Safety was assessed using CTCAE v5.0 criteria, and efficacy was assessed by objective response rate (ORR) using RECIST v1.1 criteria. Secondary objectives included preliminary data on disease control rate (DCR), duration of response (DOR), ORR using immune RECIST criteria (iRECIST), progression free survival (PFS) and overall survival (OS). Results: Here we report the results of the dose escalation cohort. Eight pts were treated with median age 69y [60-76]; 75% male; and PS 0 (3 pts) or 1 (5 pts). Pts were White (62.5%), Asian (25%), and African American (12.5%). Six of 8 pts had underlying viral hepatitis (5 hepatitis C, 1 hepatitis B), and all pts were Child Pugh A at enrollment with median baseline alpha-fetoprotein (AFP) level 41.8 [3.8–917.2]; 4 pts received prior local therapies. A total of 91 cycles of therapy were administered; 2 pts received 27 and 43 cycles of treatment each. Six pts were evaluable for DLT; 2 pts were replaced for DLT assessment due to insufficient dose administered, unrelated to toxicity. No DLTs were observed at either the 50 or 100mg dose of BMS-986205. There were 24 treatment-related adverse events (TRAEs), 4 of which were Grade 3 events; there were no Grade 4-5 events. The most common TRAEs of all grades were AST elevation and ALT elevation in 3 pts, and diarrhea, maculopapular rash and increased alkaline phosphatase in 2 pts each. Grade 3 events were diarrhea and AST elevation (1 pt), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 pt). Eight pts were evaluable for efficacy with best response of partial response in 1 pt (12.5%) and stable disease in 3 pts (37.5%), yielding a DCR of 50%. Median PFS was 8.5 weeks; median OS has not been reached. Conclusions: Combination BMS-986205 and nivolumab showed a manageable safety profile with durable benefit as 1st line therapy in a meaningful subset of patients with unresectable/metastatic HCC. Clinical trial information: NCT03695250.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase–positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase–negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

SummaryThere have been no large studies comparing reduced‐intensity/non‐myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T‐cell non‐Hodgkin lymphoma (T‐NHL) patients undergoing allogeneic transplant (allo‐HCT). A total of 803 adults with peripheral T‐cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T‐cell lymphoma (age 18–65 years), undergoing allo‐HCT between 2008–2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79–1.29; p = 0.95). Similarly, non‐relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61–1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98–1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92–1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3–4 acute graft‐versus‐host disease (HR = 0.67; 95% CI = 0.46–0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo‐HCT for T‐cell NHL.

Abstract Mature T-cell lymphomas constitute the most common indication for allogeneic hematopoietic cell transplantation (allo-HCT) of all lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) between 2008 and 2018. Hematopoietic cell transplantation (HCT) platforms compared were posttransplant cyclophosphamide-based haploidentical (haplo-)HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in vivo T-cell depletion (MUD TCD+), and matched unrelated donor HCT without in vivo T-cell depletion (MUD TCD−). Coprimary end points were overall survival (OS) and progression-free survival (PFS); secondary end points included nonrelapse mortality (NRM), and relapse/progression incidence (RI). A total of 1942 patients were eligible (237 haplo-HCT; 911 MSD; 468 MUD TCD+; 326 MUD TCD−). Cohorts were comparable for baseline characteristics with the exception of higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. Using univariate and multivariate comparisons, OS, PFS, RI, and NRM were not significantly different among the haplo-HCT, MSD, MUD TCD+, and MUD TCD− cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%, respectively, and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared with PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma (TCL). Outcomes of haplo-HCT were comparable to those of matched donor allo-HCT.

Abstract Background Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions, such as coughing, and care activities, such as aerosol-generating procedures, likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of the personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. The purpose of the current study was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists, with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations, including 2 updated recommendations and 1 new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE by HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2, and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies.

Abstract The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Limited information exists regarding the echocardiographic and clinical predictors of exercise capacity and their effects on exercise with advancing age or by sex. We hypothesized that LV diastolic function (DF) impacts exercise capacity to a greater degree with advancing age. This was a prospective cohort study of consecutive patients undergoing routine exercise echocardiography with the Bruce protocol (n=2955). DF assessments at rest and exercise were performed. Those with echocardiographic exercise-induced ischemia and significant valvular disease were excluded. Univariate and multivariate analyses were conducted to determine the strongest echocardiographic and clinical predictors of exercise capacity (METs). Results were reported as unstandardized β coefficient (Standard Error) as outlined beside each variable. Age and sex interactions of these predictors with exercise capacity were determined. The strongest independent multivariate predictors of exercise capacity were female vs. male sex [−1.98 (0.07), p<0.0001], body mass index >30 kg/m 2 [−1.24 (0.08), p<0.0001], age per 10 year increment [−0.85 (0.01), p<0.0001], mild resting diastolic dysfunction vs. normal [−0.70 (0.10), p<0.0001], and moderate/severe resting diastolic dysfunction vs. normal [−1.3 (0.13), p<0.0001]. LV filling pressures measured by a resting E/e’ ≥ 15 [−0.42 (0.14), p=0.004] or exercise E/e’≥ 15 [−0.31 (0.14), p<0.0001] similarly predicted a reduction in exercise capacity, each in separate multivariate analyses. The impact of impaired relaxation and left ventricular filling pressures on exercise capacity increased with advancing age (p<0.001 and p=0.02 respectively), and was most marked after age 50. These predictors had a similar negative effect on exercise capacity among men and women (p=NS). In conclusion, in this large population referred for exercise echocardiography and not limited by ischemia, resting DF and resting/exercise LV filling pressures independently predicted exercise capacity. The increasingly potent effect of impaired relaxation and exercise LV filling pressures with advancing age suggest that DF plays an important role in the development of exercise intolerance in the elderly.