Evaluating implementation of NCCN guideline-directed genetic screening recommendations for patients with pancreatic ductal adenocarcinoma.

PURPOSE: In 2019, the National Comprehensive Cancer Network (NCCN) recommended genetic testing for all patients with pancreatic ductal adenocarcinoma (PDAC). To evaluate the status of implementation of these guidelines in a loco-regional setting, we performed a retrospective, observational study among patients with newly diagnosed PDAC who received oncologic care at Northeast Georgia Medical Center in Georgia. METHODS: Chart abstraction of patients with newly diagnosed PDAC from 1 January 2020 to 31 December 2021 was performed to include information on genetic testing recommendation and completion, and time from diagnosis to testing. The deidentified dataset was then analyzed using appropriate descriptive and associative statistical testing. RESULTS: Of the cohort of 109 patients, 32 (29.4%) completed genetic screening; 16 (14.7%) were screened within 10 days of diagnosis. Among the 77 (70.6%) patients who did not receive genetic screening, 45 (41.3%) were not recommended genetic screening despite treatment intent with standard of care therapy. However, 32 (29.4%) were not recommended genetic screening in conjunction with a desire to pursue palliative care/hospice/or due to terminal illness. CONCLUSIONS: The study highlighted the gap in implementation of NCCN guideline-directed genetic testing in PDAC patients as only a third underwent testing suggesting the need for systematic processes to facilitate testing. The test was more likely to be completed if done early in the course, especially soon after the diagnosis. Research is needed to explore discussing genetic testing for the large proportion of patients who are terminally ill at diagnosis where genetic screening would potentially benefit the family members.

Immune checkpoint inhibitors in lymphoma: challenges and opportunities.

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 mucin-domain 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.

Observation Versus Immediate Reinduction for Acute Myeloid Leukemia Patients With Indeterminate Day 14 Bone Marrow Results.

INTRODUCTION: The benefit of immediate reinduction chemotherapy for patients with indeterminate day 14 bone marrow results (≤ 20% cellularity and 5%-20% blasts) remains unclear. We report our experience with patients with acute myeloid leukemia (AML) with indeterminate day 14 bone marrow biopsy results treated with reinduction chemotherapy versus observation alone. MATERIALS AND METHODS: We performed a retrospective study to assess the outcomes of adult patients with newly diagnosed AML treated with or without reinduction chemotherapy for indeterminate day 14 bone marrow results. RESULTS: We identified 50 patients with indeterminate day 14 bone marrow results. Of the 50 patients, 25 (50%) had received reinduction therapy and 25 (50%) had not. Of the 50 patients, 24 (48%) had poor risk disease, 12 in the reinduction arm (10 with an abnormal karyotype and 2 with a normal karyotype with molecular abnormalities) and 12 in the observation arm (6 with an abnormal karyotype and 6 with a normal karyotype with molecular abnormalities). The overall response rate (complete remission plus complete remission with incomplete count recovery) was similar in both treatment arms (80% vs. 80%). No statistically significant difference was found in the median overall survival (13 months vs. 21 months; P = .88) or relapse-free survival (13 months vs. 33 months; P = .53) between the 2 treatment arms. CONCLUSION: Our study did not find a statistically significant difference in the overall response rates or survival outcome measures for patients with AML and indeterminate day 14 bone marrow in the 2 treatment groups. Our findings question the utility of immediate reinduction chemotherapy and raise concern regarding overtreatment in this patient population. Larger studies investigating similar outcomes are warranted to validate our clinical findings.