Immune checkpoint inhibitors (ICIs) are immunomodulatory antibodies that intensify the host immune response, thereby leading to cytotoxicity. The primary targets for checkpoint inhibition have included cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death receptor-1 (PD-1) or programmed cell death ligand-1 (PD-L1). ICIs have resulted in a change in treatment landscape of various neoplasms. Among hematologic malignancies, ICIs have been most successful in certain subtypes of lymphomas such as classic Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL).However, there have been several challenges in harnessing the host immune system through ICI use in other lymphomas. The underlying reasons for the low efficacy of ICI monotherapy in most lymphomas may include defects in antigen presentation, non-inflamed tumor microenvironment (TME), immunosuppressive metabolites, genetic factors, and an overall lack of predictive biomarkers of response. In this review, we outline the existing and ongoing studies utilizing ICI therapy in various lymphomas. We also describe the challenges leading to the lack of efficacy with ICI use and discuss potential strategies to overcome those challenges including: chimeric antigen receptor T-cell therapy (CAR-T therapy), bispecific T-cell therapy (BiTE), lymphocyte activation gene-3 (LAG-3) inhibitors, T-cell immunoglobulin and mucindomain containing-3 (TIM-3) inhibitors, vaccines, promotion of inflammatory macrophages, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi). Tumor mutational burden and interferon-gamma release assays are potential biomarkers of ICI treatment response beyond PD-L1 expression. Further collaborations between clinicians and scientists are vital to understand the immunopathology in ICI therapy in order to improve clinical outcomes.

e18282 Background: Lung cancer is the leading cause of cancer-related deaths worldwide. The USPSTF recommends annual low-dose CT chest (LDCT) for lung cancer screening in adults who meet the appropriate criteria: age 55-80, current smokers or former smokers who quit within 15years, with a 30 pack-year smoking history. Even with these recommendations, screening rates in these patients remain low. We created a study to assess compliance in an outpatient Internal Medicine clinic to assess the barriers for obtaining LDCT. We hypothesized that by providing an educational program, overall compliance would increase. Methods: The study was divided in two arms: a pre-intervention arm and a post-intervention assessment. Initially, 35 physicians completed a questionnaire on their attitudes to LDCT screening and their reasons for not screening high risk patients. We created a lung cancer screening education program, which consisted of lectures provided to physicians. Following the lectures, consecutive patient visits were reviewed to assess compliance with screening. Results: In the first arm, 678 visits were reviewed. 115 patients met USPSTF criteria of whom only 26% underwent screening with LDCT. The most common reasons for not ordering LDCT scans in patients meeting criteria included: poor knowledge of criteria (22%), failure to determine if patients qualified (13%), patient refusal (8%). Following the education, 208 patients out of the 955 visits reviewed met USPSTF criteria, of which 78% underwent LDCT. Our study showed how after education, physicians were ten times more likely to screen patients for lung cancer (Odds ratio 9.98, 95% CI 5.87-16.94, p < 0.0001). Conclusions: We confirmed there was suboptimal adherence to established LDCT lung cancer screening guidelines, mainly due to unfamiliarity with the screening criteria. By providing educational lectures, compliance improved significantly. We concluded that educating physicians about lung cancer screening guidelines increased LDCT screening tenfold, and therefore benefit patients that are at high risk for developing lung cancer.

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