Baldeo, Candice

Abstract INTRODUCTION: Autologous hematopoietic stem cell transplantation can heavily impact the quality of life (QOL) of an individual. However, this procedure may be the only hope for a cure or a longer life for some individuals. When these patients develop severe neutropenia during transplantation, protective isolation is recommended to reduce the risk of infection. During protective isolation, patients may be confined to their hospital room which can decrease their physical activity. For autologous hematopoietic stem cell receipts (AHSCR), severe neutropenia may last several days to weeks. During this time, patients often experience social isolation, emotional encumbrances and also physical deconditioning.Data is inconsistent whether protective isolation does reduce the incidence of infections. In this study, we sought to investigate the impact of physical activity during hospitalization on Quality of Life in AHSCR with severe neutropenia using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire. METHODS: We conducted a prospective observational study of 15 patients admitted to Mayo Clinic Florida during November 2017 to May 2018 for autologous hematopoietic stem cell transplantation, wherein we monitored the activity of each patient during hospitalization by recording the number of steps taken each day by using an activity tracker worn by the patient. Informed consent was obtained on admission before enrolling patients. Patients completed a Quality of Life (QOL) questionnaire (FACT-BMT version 4) on admission and prior to discharge from the hospital. RESULTS: Of the 15 patients that were enrolled, 5 walked ≤ 100 steps/day (group A, median, 71) and 10 walked > 100 steps/day (group B, median, 406). While there was no difference in the median time to engraftment and length of hospital stay, the mean QOL score decreased from 89.2 on admission to 81.4 on discharge in less active neutropenia patients compared to the ones who were more active. (Table 1; Figure 1) CONCLUSION: Lack of physical activity decreases QOL in AHSCR. During hospitalization, AHSCR should be encouraged to increase their activity to improve QOL. Having an activity tracker may make it easier for patients to monitor their activity, and thus lead to a better QOL. Figure. Figure. Disclosures Sher: Affimed: Research Funding. Ailawadhi:Pharmacyclics: Research Funding; Janssen: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy.

Introduction: Pharmacogenomics is about selecting the “right drug in the right amount for the right patient.” In metastatic colorectal cancer, germline pharmacogenomics testing presents a unique opportunity to improve outcomes, since the genes dihydropyrimidine dehydrogenase and UDP-glucuronosyltransferase metabolizing the chemotherapy drugs, 5-fluorouracil, and irinotecan are already well known. In a retrospective analysis of the landmark TRIBE clinical trial [(TRIBE - TRIplet plus BEvacizumab multicenter, phase III trial by the Italian Cooperative GONO (Gruppo Oncologico Nord Ovest) group (NCT00719797)], the proportion of patients with serious adverse events was higher in those with dihydropyrimidine dehydrogenase/UDP-glucuronosyltransferase aberrations and was dose dependent. We aimed to report on the feasibility and the results of incorporating pharmacogenomics testing into clinical practice. Methods: As a quality improvement initiative and a center of individualized medicine grant, we integrated the use of OneOme RightMed comprehensive test, which reports on 27 genes related to pharmacogenomics and over 300 medications of interest. We limited initial testing to patients with colorectal cancer. Pharmacists provided dosage recommendations based on test results in real-time. Results: At our cancer center, 155 patients underwent pharmacogenomics testing from November 2017 to January 2019. Results were available within 3 to 5 days of testing for most patients and were integrated into treatment decision-making. Of 155 sampled participants, a total of 89 (57.4%) participants had an UGT1A1 variant genotype, NM_000463.2: c.-53_-52[8] *1/*28, n = 74 (47.7%); *28/*28, n = 15 (9.7%). Additionally, 4 (2.6%) participants were heterozygous for dihydropyrimidine dehydrogenase. Two (1.3%) individuals were heterozygous for both UDP-glucuronosyltransferase and dihydropyrimidine dehydrogenase genes. All (100%) the patients had at least 1 actionable aberration related to supportive care medications ( CYP-family) of all the possible medications listed on their pharmacogenomics report. Conclusion: Preemptive comprehensive pharmacogenomics testing can be integrated into clinical practice in real-time for patients with cancer given faster turnaround and low cost. Pharmacist-driven, patient-specific medication management consults add further value given the number of genes/drugs. This sets the stage for a prospective randomized clinical trial to demonstrate the amount of benefit this can result in these patients.

122 Background: Mixed response (MR) to systemic therapy is common and associated with a poor prognosis. MR often represents a therapeutic dilemma resulting in the discontinuation of a therapy to which a portion of the tumor is still sensitive, due to the emergence of resistance in other metastatic deposits. We hypothesize that discordant responses in patients receiving immunotherapy may be associated with genomic variation within discordant tumors. Methods: We defined MR with the following criteria: 1) At least one tumor has increased in size while another tumor has decreased; 2) One or more tumors have remained stable while another has increased; 3) One or more tumors have remained stable while another has decreased. 4) A new tumor has developed while other tumors have decreased or remained stable. Between 2012 and 2017, we identified 112 patients with a MR. Two patients with metastatic lung cancer, treated with nivolumab underwent paired, simultaneous sampling of discordant tumors. Results: Both patients treated with nivolumab demonstrated genomic heterogeneity between discordant tumors on next-generation sequencing, including one patient with SCLC. Conclusions: MR remains a common and challenging therapeutic quandary. Genomic heterogeneity and differences in TMB of metastatic tumors demonstrating a MR, may be factors that contribute to this phenomenon. Further characterization of genomic discrepancies in MR may provide insights into mechanisms of emerging resistance, as well as, more rational and effective combinatorial therapies.[Table: see text]

Introduction: Individuals receiving systemic anticancer therapies for advanced solid tumors routinely undergo imaging studies to assess the efficacy of the treatment. Mixed response (MR) to cancer therapy is a common but poorly described phenomenon. There is a paucity of data regarding both the incidence and possible mechanisms of this clinical quandary. Potential etiologies include tumor heterogeneity, differences in tumor microenvironment, and discrepancies in drug delivery to different tumor deposits. It is also possible that MR simply reflects differences in the rate of resistance emerging. MR represents a therapeutic dilemma for the clinician. Methods: Mixed tumor response was defined as: One tumor decreasing in size; one tumor increasing in size (classified as RECIST response/progressions), One tumor stable; another tumor progressing, One tumor stable; another tumor responding, New tumor; another tumor responding or remaining stable. Between 2015 and 2017, 120 restaging CT scans were reviewed of patients who had received at least 1 line of therapy for advanced cancer diagnosis which showed MR; hematologic malignancies were excluded. Charts were reviewed to determine the clinical decision that was made at the time of the MR. Results: A total of 120 scans with MR were reviewed from various solid tumor diagnoses. 38 scans were excluded due to loss of follow-up or death. Of the remaining 82 scans, therapy was switched in 30, the same therapy was continued in 50, and an additional agent was added to the current treatment in 2 cases (Table). Of the patients in which treatment was switched, 20% (6/30) showed response to treatment on the following scan. Of the cases that were kept on current treatment, none showed response on the following restaging scan which was done 6–8 weeks later. There were 4 (10%) deaths prior to the next scan in the group that had treatment switched and similarly 5 deaths (10%) prior to the next scan in the group in which treatment remained the same. Conclusion: MR is associated with a poor prognosis, irrespective of treatment decisions. These data are retrospective and our sample size is small, so definitive conclusions cannot be drawn. However, changing therapy when a MR is observed may be of benefit to some patients. A prospective evaluation to more accurately describe and understand the MR phenomenon is warranted.

703 Background: In metastatic colorectal cancer (CRC), pharmacogenomics (PGx) testing presents a unique opportunity to improve outcomes since the genes DPYD & UGT1A1 encoding the enzymes metabolizing the chemotherapy drugs, 5-fluorouracil and irinotecan, are already well known. In the TRIBE clinical trial, proportion of patients with serious adverse events (SAEs) was higher in those with DPYD/UGT1A1 aberrations and were dose dependent. Critical barrier has been integration into clinical practice. We aimed to report on the feasibility and results of incorporating PGx testing into clinical practice. Methods: As a quality improvement initiative, we integrated the use of OneOme RightMed comprehensive test through funding from our center of individualized medicine, which reports on 28 genes and over 350 medications of interest. Pharmacists provided dosage recommendations based on test results real-time. Results: 126 patients have had the PGx testing since November 2017. Results have been available within 3-5 days. The table outlines the analyzed results thus far of variants in UGT1A1 and the DPYD-genes alongside the CYP450 genes. Of these, 59% had a DPYD/UGT1A1 aberration and 100% had at least one actionable aberration related to supportive care medications from all possible medications listed on their PGx report. Conclusions: Preemptive comprehensive PGx testing can be integrated into clinical practice in real-time for cancer patients. This sets the stage for a prospective randomized clinical trial to demonstrate the amount of benefit this can result in these patients. [Table: see text]

660 Background: Adverse toxicities to chemotherapy remain a limiting factor for patients receiving treatment for malignancies. In gastrointestinal cancers, particularly metastatic colorectal cancer, the majority of front line treatment remains chemotherapy containing 5-fluorouracil and/or irinotecan. One particular cause that can predispose a patient to increased toxicity from 5-fluorouracil is genetic variation in the DPYD gene, as well as TYMS gene. Similarly, genetic variation in the UGT1A1 gene can increase the risk of irinotecan toxicity. These gene variations may have major implications when deciding on treatment regimens for these types of patients; however, they are not routinely checked. Methods: In Mayo Clinic Florida, patients with metastatic colorectal cancer receiving 5-fluorouracil and/or irinotecan chemotherapy during the period of July 2017-July 2018 were tested for genetic variants in DPYD/TYMS and UGT1A1. This testing was done during routine clinic visit either by buccal swab or blood test. The DPYD/TYMS and UGT1A1 variant results were evaluated together with a pharmacist for recommendations regarding dose reductions on 5-fluorouracil and irinotecan respectively. Results: A total of 292 patients were tested. Total number of patients who had a variation in the DPYD/ TYMS and/or UGT1A1 gene was 169 (57.9%). The UGT1A1 variation was the most prevalent with 154 (52.7%) patients having a variant (115 heterozygous variant, 34 homozygous variant and 5 double heterozygous variant). Specifically there were 3 patients with both UGT1A1 and DPYD variants and 3 patients with both UGT1A1 and TYMS variants. One patient had both DPYD and TYMS variations. Conclusions: Routine pharmacogenomic testing for UGT1A1 and DPYD/TYMS genetic variants should be done in all patients receiving irinotecan and 5-fluorouracil chemotherapy respectively. Avoiding or preemptively dose reducing these agents in patients with gene variations may help prevent toxic adverse events and make treatment more tolerable.

814 Background: The importance of pharmacogenomics in optimizing drug doses and avoiding adverse events is increasingly being recognized. The FDA has listed pharmacogenomic biomarkers as part of drug labeling in many medications including chemotherapies such as 5-fluorouracil and irinotecan. Pharmacogenomics may enable selection of the most tolerable treatment without compromising treatment success. Variation in the dihydropyrimidine dehydrogenase ( DPYD) and UGT1A1 gene mutations can increase the risk of 5-FU and irinotecan based chemotherapy respectively. Also, the feasibility of testing in real-time and incorporating results into management has not been demonstrated. The focus of our study was to demonstrate this in the real world scenario as a quality improvement project. Methods: In July-August 2017, 89 patients who were on irinotecan and/or 5-FU chemotherapy were tested for DPYD and UGT1A1 genetic variations at Mayo Clinic Florida. Testing was done through blood sample which was collected at routine clinic visit prior to starting therapy or in patients already receiving chemotherapy. Pharmacy electronic consultation was obtained for recommendations regarding current and/or future chemotherapy regimens, based on pharmacogenomics results. A medication therapy management (MTM) consultation from the pharmacist was incorporated and included into the patient’s chart. Results: Total number of patients who has some variation in the UGT1A1 and/or DPYD gene was 60 (67%). Specifically, there were 12 patients who were homozygous for the UGT1A1 gene and 3 homozygous for DPYD gene. Both genes were affected in 3 patients. One patient was triple heterozygous for DPYD and homozygous for UGT1A1. Pharmacogenomic results were obtained for these patients within 5 business days. Conclusions: A higher prevalence of UGT1A1 and DPYD variants were reported in our patient cohort tested than what is reported in the literature. Additionally, we were able to obtain results for these patients in a timely fashion. This was then further incorporated into medication therapy management consultation from the pharmacist, which added further value.

Abstract Colorectal carcinoma is the third most common cancer worldwide. Approximately 20% of patients with colorectal cancer will have metastatic disease at the time of initial diagnosis, and approximately 30% to 50% of patients with primary colon cancer will relapse and die of metastatic cancer. The 5-year survival rate of metastatic colorectal cancer remains disappointing at approximately 10%. Angiogenesis plays a significant role in tumor growth and metastasis in colorectal carcinoma. There are currently 4 US Food and Drug Administration–approved antiangiogenic agents for metastatic colorectal cancer. Bevacizumab is the only antiangiogenic agent approved by the US Food and Drug Administration for first-line treatment of metastatic colorectal cancer. Other antiangiogenic agents include ramucirumab, ziv-aflibercept, and regorafenib. We review the data supporting the use of antiangiogenics in this disease.