Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness. Patient 1 was worked up for health care-associated pneumonia, as well as acute sinusitis prior to the diagnosis of cryptococcal meningoencephalitis. He also had a more complex past medical history than patient 2. Patient 2 developed atrial fibrillation from ibrutinib prior to admission for presumed health care-associated pneumonia. Cryptococcal antigen testing was done sooner in this patient due to patient receiving high-dose steroids for the treatment of underlying hemolytic anemia. We conclude that patients who develop acute illness while receiving ibrutinib should be considered for cryptococcal antigen testing.

<b><i>Introduction:</i></b> Trastuzumab deruxtecan is a monoclonal antibody linked to a chemotherapy moiety that was recently approved by the Food and Drug Administration (FDA) for the treatment of metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancers. There are labeled black box warnings for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. Additionally, chemotherapy-induced nausea and vomiting (CINV) was reported to be as high as 78% (∼8% grade 3 or higher) in phase I and II clinical trials. Clinical trial and package insert recommendations for the management of CINV are not available, making real-world management difficult. <b><i>Case Presentation:</i></b> We reviewed the first 10 patients who received trastuzumab deruxtecan at our hospital-based community cancer center to determine if CINV management was adequate. We found a rate of 28.9% CINV (all grade 1 and 2) despite treatment as a moderate emetic potential regimen. Interventions by the treatment team to manage trastuzumab deruxtecan as a high-risk emetic regimen resulted in reduced CINV and ongoing treatment for all patients. <b><i>Discussion and Conclusion:</i></b> This review indicates that management of CINV for patients receiving trastuzumab deruxtecan should follow recommendations for regimens with a high-risk emetic potential.

254 Background: A systematic grading system was created to evaluate literature submitted with off-label requests to the Inova Schar Cancer Institute (ISCI) oncology P&T. Level of evidence (LOE) 1A, 1B, and 1C are granted immediate approval. LOE 2A, 2B, 2C require two members (MD and PharmD) to approve. LOE 3A, 3B, 3C require 3/4 (2MDs, 2PharmDs) members to approve. LOE no benefit (NB) is denied approval. Methods: Identified off-label requests for hematology/oncology patients from December 23, 2016 to January 2, 2019. Primary objective was retrospective evaluation of literature submitted using a systematic grading system through the oncology P&T. Secondary objective was to evaluate financial and clinical outcomes of off-label treatments, including compliance with Quality Oncology Practice Initiative measures. Future aim is to compare LOE and treatment outcomes pre- and post-implementation. Results: There were 73 off-label requests with 126 references submitted as supporting literature. The most frequently requested treatments were nivolumab (21.9%) and pembrolizumab (20.5%). The most common disease state was breast cancer. The LOE for the literature submitted was 1A (10.3%), 1B (23%), 1C (8.7%), 2A (9.5%), 2B (7.9%), 2C (4.8%), 3A (1.6%), 3B (7.1%), 3C (5.6%), and NB (21.4%). Sixty-six treatments were approved and 54 patients received at least one dose of off-label treatment. Thirty off-label requests were made based on molecular tumor board recommendations. Off-label treatment was discontinued for disease progression (29.6%), toxicity (25.9%), or death (14.8%). Three patients completed therapy and 11 received subsequent treatment after discontinuation of the off-label treatment. Average time from last treatment to death was 41.8 days (median 21, range 6-175). Eleven of 55 expired patients received hospice care prior to expiring. Most off-label treatments were approved by third party insurance (55.6%) while 37% were covered by manufacturer provided free drug and 7.4% were paid for by the ISCI Foundation. Conclusions: The standardized grading system for off-label treatments can be implemented to ensure safe and effective use of off-label treatments in oncology patients.

569 Background: Pharmacogenomics, the study of the interaction between the patient’s genome and therapeutic drug response, evaluates the associations between efficacy and toxicity through analysis of drug metabolizing enzymes. As personalized medicine advances to the forefront of cancer care, pharmacogenomics can evaluate the individual’s ability to metabolize key medications in breast cancer treatment including anti-emetics, opioids, and tamoxifen. Women who do not achieve optimal levels of the active metabolites of tamoxifen are at higher risk of recurrence. Patients on chemotherapy who do not respond to anti-emetics can suffer from nausea and vomiting resulting in dehydration and hospitalization. This project evaluates the feasibility and therapeutic impact of real time pharmacogenomics in a selection of patients at the Inova Schar Cancer Institute (ISCI). Methods: An interdisciplinary team was created through the ISCI and the Inova Translational Medicine Institute to implement cheek swab based pharmacogenomic testing in 50 new patients undergoing mastectomy or neoadjuvant chemotherapy for breast cancer. Study patients were assessed for genotypic variability of key CYP enzymes and resulting impact on anti-emetic choices, perioperative pain control, and tamoxifen use. Results: Data was collected in a RedCap database. The 50 women enrolled were ages 28-83. Cheek swabs were performed in clinic and median turn around time was 7 days. 24 distinct genotypes were found in the 50 patients. 20% had abnormal CYP2D6 phenotypes indicating abnormalities in tamoxifen metabolism. 28% of patients had results leading to changes in dose or medication choice of perioperative pain control. 6% of patients had a CYP2D6 ultra-rapid metabolizer phenotype and were given granisetron in lieu of ondansetron. These patients had no documented nausea or vomiting requiring dose adjustments to the treatment plan or medical intervention. 40% of patients had results recommending avoidance of tamoxifen, 75% of which have ER+ breast cancer. 25% of patients had recommended changes to the dose of tamoxifen. Conclusions: Pharmacogenomic testing is feasible and available real-time for immediate use in the clinic. CYP mutations impact treatment decisions in a significant proportion of patients. Individualized treatment plans tailored to pharmacogenomic recommendations can be created in the multi-disciplinary setting and may decrease side effects of treatment and improve efficacy of curative therapy.