Leighton Elliott

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole cell-based vaccines and dendritic cell-based vaccines. These therapeutic vaccines have shown acceptable safety profiles, but consistent clinical responses remain elusive despite robust immunological reactions. Combining vaccines with immunotherapeutic agents holds promise and requires further investigation. Herein, we highlight therapeutic vaccine trials while reviewing challenges and future directions of successful vaccination strategies in MDS.

10599 Background: Pancreatic cancer is the 7th most common cause of cancer death worldwide and is projected to be the second leading cause of cancer death in the next decade. Personalized care is becoming more of a reality with pharmacological regimens targeting specific genetic mutations. In March 2019, the National Comprehensive Cancer Network (NCCN) guidelines were updated to recommend germline testing (GT) in all patients with pancreatic adenocarcinoma (PDAC) considering 1 in 10 may have a germline mutation (GM). The goal of this study was to quantify compliance with these recently updated guidelines. Methods: The electronic medical records and survivorship data of all patients diagnosed with PDAC between January 1, 2017 and October 1, 2020 were reviewed. April 1, 2019 was used as the transition point (TP) for guideline updates. Descriptive statistics for all variables were determined. The rate of ordered referrals to genetic counseling (GC), as well as completion rate, was calculated. Results: A total of 304 patients were diagnosed with PDAC during the study period (223 prior to the TP). A total of 54 patients were referred for GC and 41 had GT ordered. The rate of GC referrals ordered after the TP was significantly higher than before the TP (22/81, 26.6% vs. 32/223, 14.4%; p-value 0.010). Almost 60% of patients who had genetic evaluation had private insurance. The patients who completed GT were significantly more likely to have a documented family history of cancer (61.0% vs 4.2%; p-value <.0001Patients who completed GT had more problems on their problem list (median 10 vs 7, p = 0.001). The median overall survival (OS) for all patients in the study was 7.8 months (95% CI: 6.3-9.8). Conclusions: Overall compliance with the updated NCCN guidelines significantly improved; however, it was below 25%. This study showed that there may be some lingering bias toward GT in PDAC solely for those who have a family history of cancer. Although patients with stage IV PDAC have poor outcomes, GT may still improve surveillance for family members. The approval of olaparib in patients with BRCA1/2 mutations based on the POLO trial is likely to increase provider compliance as it provides a viable maintenance strategy in these patients. Patient complexity was unlikely to affect GT rate. Assessment of provider awareness was outside the scope of this study. There is need for continued advocacy for awareness and implementation of guidelines that highlight the importance of germline evaluation on prevention, surveillance, and treatment in pancreatic adenocarcinoma.