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Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL).The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy.Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%).SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making.

Small-volume biopsies (SVBs) including fine-needle aspiration (FNA), cell block, and needle core biopsies (NCB) are increasingly utilized to diagnose and guide the clinical management of lymphoma. We established a multi-institutional interdisciplinary collaboration of cytopathologists, hematopathologists, and oncologists focused on the role of SVB in the management of patients with follicular lymphoma (FL). To assess the performance characteristics of SVB in this setting, we evaluated all consecutive SVBs performed for clinical indications of initial diagnosis, recurrence, or transformation of FL over a 5-year period and focused on the 182 that had at least one subsequent biopsy within 3 months as part of the same clinical work-up. The most common outcome of a subsequent biopsy as part of the same clinical work-up was a more specific diagnosis usually assigning the pathologic grade (111/182, 61%), followed by a complete agreement with the SVB (24/182, 13%), and change from nondiagnostic on initial biopsy to diagnostic on subsequent biopsy (21/182, 12%). A minority resulted in a diagnostic change from benign to lymphoma (17/182, 9%), a change in FL grade (5/182, 3%), or change in the lymphoma diagnostic category (4/182, 2%). There were no cases where an initial diagnosis of lymphoma was overturned. The distribution of discrepancies was similar across initial SVB types (FNA, FNA + cell block, NCB with or without FNA). Tissue limitations were noted in a minority of cases (53/182, 29%) and were enriched among initially nondiagnostic biopsies (16/21, 76%). Flow cytometry immunophenotyping was performed in the majority of cases both at the first and last biopsy (147/182, 81%). SVB can be a powerful method to detect FL in various clinical indications, with discrepant cases mostly resulting from a refinement in the initial diagnosis.

An enhanced understanding of the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has opened the door to clinical trials evaluating novel agents with subtype-specific activity. It is an emerging question whether core needle biopsies (CNB) can adequately meet the increasing tissue requirements of these clinical trials. This can potentially lead to selective enrollment of patients who can undergo excisional biopsy (EB). It is also important to know whether patients who can undergo extensive diagnostic work up differ in their disease characteristics and outcomes from those who cannot. In this observational study, we describe the characteristics, outcomes, and adequacy of diagnostic tissue in patients with newly diagnosed DLBCL and primary mediastinal large B-cell lymphoma who underwent EB vs CNB. Of the 1061 patients, 532 (49.8%) underwent EB and 529 (50.1%) underwent CNB. A significantly higher proportion of patients with CNB had advanced stage disease, an international prognostic index of ≥3, and inadequate tissue for molecular analyses. Patients with CNB had significantly worse 5-year event-free survival (67.6% vs 56.9%; hazard ratio [HR], 0.76; confidence interval [CI]95, 0.6-0.9, P < .001) and 5-year overall survival (76.4% vs 69.2%; HR, 0.8; CI95, 0.6-0.9, P < .001). Thus, patients who underwent CNB have poor-risk features and inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses, and might not meet the tissue requirements of biomarker-driven clinical trials. Thus, the increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of patients with high-risk DLBCL who need novel agents.

PURPOSE The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource individual patient data from the Hodgkin Lymphoma International Study for Individual Care consortium, we developed and validated a modern clinical prediction model. METHODS Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. RESULTS The median age in the development cohort was 33 (18-65) years; nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. CONCLUSION We rigorously developed and externally validated a clinical prediction model in > 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for individualized point-of-care use.

Objectives Small-volume biopsy—fine-needle aspiration biopsy (FNAB) with or without core biopsy—is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out. Methods This study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated. Results Most respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma. Conclusions This survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.

Agents targeting the unique biology of mycosis fungoides and Sézary syndrome are quickly being incorporated into clinical management. With these new therapies, we are now capable of inducing more durable responses and even complete remissions in advanced disease, outcomes which were exceedingly rare with prior therapies. Yet, even this new generation of therapies typically produce objective responses in only a minority of patients. As our therapeutic options increase, we are now challenged with selecting treatments from a growing list of options. To gain the full benefit of these novel agents, we must develop strategies to match treatments for the patients most likely to benefit from them. Here, we consider both the current approaches to treatment selection based on clinical features and the future of molecular biomarker-guided therapy for patients with this heterogeneous disease.

Purpose Combined modality therapy (CMT) is standard therapy for early-stage Hodgkin lymphoma (ESHL). We previously reported excellent outcomes with the abbreviated Stanford V regimen. Herein we report updated results with median follow-up >10 years on survival, therapy-related late effects, and impact of disease risk factors on patient outcomes. Methods and Materials The G4 and G5 studies enrolled patients with stage I-IIA nonbulky ESHL. Patients received 8 weeks of Stanford V chemotherapy followed by 30 Gy modified involved-field radiation therapy (mIFRT) (G4) or Stanford V-C + 20 Gy mIFRT (G5). Patients were categorized as favorable or unfavorable risk per German Hodgkin Study Group (GHSG) criteria and outcomes between groups compared. Results A total of 129 patients were enrolled (68 favorable and 61 unfavorable risk). In the G4 study (n = 87), at median follow-up of 19.7 years, 5-, 10-, and 15-year progression-free survival (PFS) and overall survival (OS) were 95.4%/97.7%, 91.8%/96.5%, and 91.8%/95.3%, respectively. In the G5 study (n = 42), at median follow-up of 13.5 years, the 5-, 10-, and 15-year PFS and OS were 92.9%/100%, 92.9%/100%, and 88.4%/91.9%, respectively. PFS (P = .86) and OS (P = .86) were not significantly different between studies. There were also no significant differences between studies in patients with favorable or unfavorable risk for PFS (F: P = .53; U: P = .96), OS (F: P = .99; U: P = .78), secondary malignancies (F: P = .74; U: P = 1.0), and cardiovascular complications (F: no cases; U: P = 1.0). Conclusions The G4 and G5 studies achieve high rates of durable remission; 20 versus 30 Gy mIFRT and cyclophosphamide substituted for mechlorethamine did not compromise nodal control, PFS, or OS in both favorable and unfavorable risk disease. These results support the efficacy of CMT in early-stage disease and lower-dose radiation therapy in patients with favorable and nonbulky unfavorable ESHL.

In a multicenter, phase II investigator-initiated trial of sequential pembrolizumab and AVD, nearly two-thirds of patients with untreated unfavorable or advanced stage classic Hodgkin Lymphoma (cHL) achieved PET-defined complete or near complete metabolic responses (CMR) following 3 doses of pembrolizumab monotherapy. Furthermore, all achieved CMR following 2 cycles of AVD chemotherapy and 100% of patients were alive without relapse at the time of initial publication. We now report long-term follow-up, including 3-year OS and planned correlative analyses. Thirty patients received single agent pembrolizumab every 3 weeks x 3, followed by AVD chemotherapy for 4-6 cycles depending on stage and bulk. PET/CT scan was performed after pembrolizumab monotherapy, 2 cycles of AVD, and at the end of therapy. Baseline biopsy samples were analyzed for genomic alterations of chromosome 9p24.1 and PD-1 pathway markers by immunohistochemistry. At a median follow up of 33.1 months (range, 26.0-43.0), PFS and OS remain 100%. All patients had genomic alterations in 9p24.1 and were positive for PD-L1 by immunohistochemistry. There was no relationship between response to single agent pembrolizumumab measured by decline in metabolic tumor volume and 9p24.1 alterations or PD-1 pathway H-scores. With additional follow-up, sequential pembrolizumab and AVD remains highly effective. The high response rates observed at all PD-ligand levels suggest that even low levels of PD ligand expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase II trial (NCT05008224) to confirm these findings is ongoing.

Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively

Background and objectives Inappropriate platelet transfusions represent an opportunity for improvements in patient care. Use of a best practice alert (BPA) as clinical decision support (CDS) for red cell transfusions has successfully reduced unnecessary red blood cell (RBC) transfusions in prior studies. We studied the impact of a platelet transfusion BPA with visibility randomized by patient chart. Materials and methods A BPA was built to introduce CDS at the time of platelet ordering in the electronic health record. Alert visibility was randomized at the patient encounter level. BPA eligible platelet transfusions for patients with both visible and non-visible alerts were recorded along with reasons given for override of the BPA. Focused interviews were performed with providers who interacted with the BPA to assess its impact on their decision making. Results Over a 9-month study period, 446 patient charts were randomized. The visible alert group used 25.3% fewer BPA eligible platelets. Mean monthly usage of platelets eligible for BPA display was 65.7 for the control group and 49.1 for the visible alert group (p = 0.07). BPA-eligible platelets used per inpatient day at risk per month were not significantly different between groups (2.4 vs. 2.1, p = 0.53). Conclusion It is feasible to study CDS via chart-based randomization. A platelet BPA reduced total platelets used over the study period and may have resulted in $151,069 in yearly savings, although there were no differences when adjusted for inpatient days at risk. During interviews, providers offered additional workflow insights allowing further improvement of CDS for platelet transfusions.

We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale–Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell’s palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

Background: Genomic copy number alterations (CNAs) of chromosome 9p24.1 characterize classic Hodgkin lymphoma (cHL) leading to increased expression of programmed cell death ligands -1 and -2 (PD-L1 and PD-L2). Amplifications and high level copy number gains (CNG) have been associated with advanced stage cHL and inferior treatment outcomes with standard chemotherapy. Few studies have assessed 9p24.1 genomic alterations in the frontline setting in the context of PD-1 blockade monotherapy. We conducted a phase 2 clinical trial of sequential pembrolizumab (PEM) x 3 followed by doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy (4-6 cycles) in newly diagnosed cHL. Interim response to single agent PEM was assessed by PET-CT and by decline in metabolic tumor volume (MTV). Herein, we report updates after extended follow-up of patients (median 33.1 months), and results of correlative studies analyzing 9p24.1 CNAs and PD-1 pathway expression. Methods: Pre-treatment diagnostic biopsy specimens were double stained for PD-L1 (E1L3N, XP Cell Signaling) and PAX5, single stained for PD-L2 and pSTAT3, and scored by two expert hematopathologists (QC, LBS) for percentage positive cells and intensity of staining. A modified H score was calculated as the product of staining intensity (0-3) and percentage of positive tumor cells (0-100%), ranging from 0 - 300 was calculated for PD-L1, PD-L2, and pSTAT3. Fluorescence in situ hybridization (FISH) to assess chromosome 9p24.1 CNAs was performed by co-hybridizing PD-L1/PD-L2 probes (target) with the centromeric 9 probe (control). In each case, the percentage and magnitude of 9p24.1 CNAs were evaluated. Four FISH categories were defined based on the target:control ratio and total copy numbers (CNs) of the target per Hodgkin Reed-Sternberg (HRS) cell to include: amplification (ratio≥3), copy number gain (CNGs) (1≤ratio The relationships between PD-1 pathway markers, genomic alterations, and response to single agent PEM by MTV were assessed statistically using Fisher's Exact test, Kruskal-Wallis test, or Spearman's rank correlation as appropriate. PD-L1 H Scores were grouped into terciles of approximately equal size for categorical analysis. Response was defined as a complete metabolic response (CMR), ≥ 90% reduction in MTV (near CMR), or partial response with < 90% reduction by MTV (PR). Kaplan-Meier curves were used to analyze progression-free survival (PFS) and overall survival (OS). Results: Thirty patients were enrolled from September 2017 through August 1, 2019; 28 had tissue available for FISH analysis and 29 for immunohistochemistry. Patient responses to single agent PEM were PMR in 11 (36.7%), near-CMR in 8 (26.7%), and CMR in 11 (36.7%). CMR rate following AVD x 2 was 100%. With the extended follow-up (median 33.1 months, range 26.0-43.0), PFS and OS both remained at 100% (Figures 1a, 1b). Among 28 cases with available FISH analysis, all patients demonstrated genomic alterations in 9p24.1. The highest level alteration was amplification in 14 patients (50%) and copy number gain in 14 (50.0%) Six of 22 examined cases were EBER-positive. Forty-one percent (n=7) of patients with a CMR or near CMR had amplifications in 9p24.1, compared to 64% (n=7) with a PMR following PEM monotherapy (p=0.2). The median PD-L1 H score was 215 (range 20-300). Of 29 patients assessed, 28% had PD-L1 H scores in the first tercile (H-score 1-190), 34% in the second tercile (190-240), and 38% in the third tercile (240-300). There was no association between response to single agent PEM and 9p24.1 alteration, PD-L1, PD-L2 or STAT3 H-scores, % residual disomy, or EBER status (see Figure 1c for PD-L1 results). Conclusions: We found that after extended follow-up, sequential pembrolizumab and AVD chemotherapy remains a highly effective strategy with 100% of patients remaining alive without relapse. The high response rates observed at all PD-L1/PD-L2 levels in this clinical study suggest that even low levels of PD ligand expression may be sufficient for response to PD-1 blockade in previously untreated cHL. We gratefully acknowledge support from Merck & Co. Figure 1 Figure 1. Disclosures Allen: Kyowa Kirin: Consultancy; Secure Bio: Consultancy; ADC Therapeutics: Consultancy; MorphoSys: Consultancy; Epizyme: Consultancy. Advani: Astellas/Agensys: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Cell Medica: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Millenium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy; Regeneron: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Gordon: Zylem Biosciences: Patents & Royalties: Patents, No royalties; Bristol Myers Squibb: Honoraria, Research Funding. Winter: Actinium Pharma: Consultancy; BMS: Other: Husband: Data and Safety Monitoring Board; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Epizyme: Other: Husband: Data and Safety Monitoring Board; Agios: Other: Husband: Consultancy; Gilead: Other: Husband: Consultancy; Janssen: Other: Husband: Consultancy; Karyopharm (Curio Science): Honoraria; Merck: Consultancy, Honoraria, Research Funding.

Small-volume biopsy-fine-needle aspiration biopsy (FNAB) with or without core biopsy-is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out.This study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated.Most respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma.This survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.

Laboratory costs of thrombophilia testing exceed an estimated $650 million (in US dollars) annually. Quantifying the prevalence and financial impact of potentially inappropriate testing in the inpatient hospital setting represents an integral component of the effort to reduce healthcare expenditures. We conducted a retrospective analysis of our electronic medical record to evaluate 2 years' worth of inpatient thrombophilia testing measured against preformulated appropriateness criteria. Cost data were obtained from the Centers for Medicare and Medicaid Services 2016 Clinical Laboratory Fee Schedule. Of the 1817 orders analyzed, 777 (42.7%) were potentially inappropriate, with an associated cost of $40,422. The tests most frequently inappropriately ordered were Factor V Leiden, prothrombin gene mutation, protein C and S activity levels, antithrombin activity levels, and the lupus anticoagulant. Potentially inappropriate thrombophilia testing is common and costly. These data demonstrate a need for institution-wide changes in order to reduce unnecessary expenditures and improve patient care.

Background: Chromosome 9p24.1/PD-L1/PD-L2 genomic copy number alterations (CNAs) including amplifications and copy number gains (CNGs) are predominant features of classic Hodgkin lymphoma (cHL) and lead to overexpression of the programmed death-1 (PD-1) ligands 1 and 2 (PD-L1 and PD-L2). Amplifications and high level CNGs have been associated with advanced stage cHL and inferior treatment outcomes with standard chemotherapy. There are few studies that correlate 9p24.1/PD-L1/PD-L2 amplifications or CNGs with response to PD-1 blockade monotherapy in the frontline setting. We conducted a phase 2 clinical trial of sequential pembrolizumab (PEM) x 3 followed by doxorubicin, vinblastine, dacarbazine (AVD) chemotherapy (4-6 cycles) for newly diagnosed cHL. Interim response to single agent PEM was assessed by PET-CT and by decline in metabolic tumor volume (MTV). Herein, we report the results of correlative studies analyzing 9p24.1 CNAs, PD-1 pathway expression and response to PD-1 blockade. Methods: Pre-treatment diagnostic biopsy specimens were double stained for PD-L1 (E1L3N, XP Cell Signaling) and PAX5, single stained for PD-L2 and pSTAT3, and scored by two expert hematopathologists (QC, LBS) for percentage positive cells and intensity of staining. A modified H score was calculated as the product of staining intensity (0-3) and percentage of positive tumor cells (0-100%), ranging from 0 - 300. Fluorescence in situ hybridization to assess (FISH) chromosome 9p24.1 CNAs was performed by co-hybridizing PD-L1/PD-L2 probes (target) with the centromeric 9 probe (control). In each case, the percentage and magnitude of 9p24.1 CNAs were evaluated. Four FISH categories were defined based on the target: control ratio and the total copy numbers (CNs) of the target per Hodgkin Reed-Sternberg (HRS) cell to include: amplification (ratio≥3, CNs≥ 6), copy number gain (CNGs) (1≤ratio Results: Thirty patients were enrolled from September 2017, through August 1, 2019; 28 had tissue available for FISH analysis and 29 for immunohistochemistry. Response to single agent PEM was PR in 11 (36.7%), near-CMR in 8 (26.7%), and CMR in 11 (36.7%). CMR rate following AVD x 2 was 100%. All patients in this analysis had genomic alterations, although 5 patients did not reach the cut off of 10%. The highest level alteration was amplification in 11 patients (36.7%), copy gain in 7 (23.3%), polysomy in 5 (16.7%) and disomy in 5 (16.7%) (Table 1). The average 9p24.1 copy number per HRS cell was 3.1 (range 2-8.1). Six of 22 examined cases were EBER-positive. There was no evidence of a statistical relationship between response to single agent PEM and 9p24.1 alteration, PD-L1, PD-L2 or STAT3 H-scores, or EBER status. We found PD-L1 H Score tercile differed statistically by FISH category (P=.024, Fisher's Exact Test). Notably, there were no patients with amplification in the lowest tercile. More compelling, we found a positive association between PD-L1 H Score and average 9p24.1 locus copy number (Spearman's ρ=.36, P=.063, Fig 1a) and a negative association between PD-L1 H Score and percent disomic cells (Spearman's ρ= -0.21, P=0.29, Fig 1b) although the statistical significance of these results was limited by the small sample size. Conclusions: Our data is consistent with prior reports indicating a positive association between 9p24.1 genetic alterations and PD-L1 expression. The high response rates observed at all PD ligand levels seen in this clinical study suggests that even low levels of PD ligand expression may be sufficient for response to PD-1 blockade in previously untreated cHL. Disclosures Allen: Bayer:Consultancy, Other;Imbrium:Consultancy, Other;Research to Practice:Speakers Bureau;Clinical Care Options:Speakers Bureau;Curio Sciences:Honoraria.Evens:Merck:Consultancy, Honoraria, Research Funding;Pharmacyclics:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;MorphoSys:Consultancy, Honoraria;Research To Practice:Honoraria, Speakers Bureau;Abbvie:Consultancy, Honoraria;Mylteni:Consultancy, Honoraria;Seattle Genetics:Consultancy, Honoraria, Research Funding;Epizyme:Consultancy, Honoraria, Research Funding.Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics:Research Funding;Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda:Consultancy.Pro:Verastem Oncology:Research Funding.Karmali:Takeda:Research Funding;BeiGene:Speakers Bureau;BMS/Celgene/Juno:Honoraria, Other, Research Funding, Speakers Bureau;Karyopharm:Honoraria;AstraZeneca:Speakers Bureau;Gilead/Kite:Honoraria, Other, Research Funding, Speakers Bureau.Gordon:Zylem Biosciences:Patents & Royalties: Patents, No Royalties.Winter:Amgen:Consultancy;Epizyme:Other: DSMB;Norvartis:Consultancy, Other: DSMB;CVS/Caremark:Consultancy;Ariad/Takeda:Consultancy;Delta Fly Pharma:Consultancy;Merck:Membership on an entity's Board of Directors or advisory committees, Other: advisory board;Karyopharm:Membership on an entity's Board of Directors or advisory committees, Other: advisory board.

e13569 Background: Progress in understanding the molecular biology of DLBCL has led to development of complex molecular classifications that rely on sequencing methods. These molecular clusters are defined by activation of distinct pathways and may aid in selecting targeted therapy. In the molecular era, tissue requirements in clinical trials have increased to ensure sufficient tissue for molecular testing, potentially resulting in bias for enrollment of patients with larger excisional biopsies (EB). We examined the impact of tissue biopsy method on outcomes of DLBCL in a prospective observational study. Methods: Consecutive adult patients with DLBCL within 9 months from their initial diagnosis were enrolled into the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). Demographics, clinical variables, type of tissue biopsy (EB vs. core needle biopsy (CNB)) for initial diagnosis and initial treatment were recorded at baseline. Pts were contacted every 6 months from the date of diagnosis for first 3 years and then annually thereafter. Study objectives were event free survival (EFS) and overall survival (OS) by tissue biopsy method. Results: A total of 1061 patients with newly diagnosed DLBCL, from 2002 to 2015, were included. The table lists baseline characteristics of the cohort. 593 (56%) pts underwent EB and 468 (44%) underwent CNB for initial diagnosis. A significantly higher proportion of patients receiving CNB had performance status >=2, advanced stage, high risk disease by international prognostic index (IPI), abnormal lactate dehydrogenase. Median time from diagnosis to treatment initiation (DTI) was significantly shorter in the CNB group (13 days) than EB group (19 days). 2-year EFS (60% vs 75%, HR 0.75 (0.6-0.9), p

Background: Pembrolizumab (PEM), an anti-PD-1 antibody is approved for the treatment of relapsed/refractory cHL based on results of a pivotal trial demonstrating an overall response rate (ORR) of 69% and 22% complete response (CR) rate. To investigate the impact of PEM monotherapy in previously untreated patients (pts), we conducted a phase 2 clinical trial of sequential PEM followed by AVD chemotherapy for untreated cHL. Herein, we report the primary analysis of response (PET2) to single agent PEM in the frontline setting and the results of interim FDG18-FDG PET-CT (PET3) following AVD x 2. Methods: Pts > 18 years of age with newly diagnosed cHL stages I-IV, including early stage pts with at least 1 risk factor according to NCCN criteria, were eligible. Pts were treated sequentially with 3 cycles of PEM at 200 mg every 3 weeks followed by an interim PET-CT (PET2) for primary analysis. Subsequently, pts received 4-6 cycles of AVD chemotherapy based on initial stage, with PET-CT's repeated after 2 cycles of AVD and at the end of therapy. There was no consolidative radiotherapy. Response to single agent PEM was assessed by Lugano criteria and decline in total metabolic tumor volume (TMV). We hypothesized that PEM monotherapy prior to AVD would result in a CR rate of 50% and would reduce the frequency of PET-positivity on the interim PET (PET3) following 2 cycles of AVD compared to prior reports. Results: Thirty pts enrolled from September 2017- March 2019 with a data cutoff of June 14, 2019. The median age of participants was 30 (range, 21-77), and 4 pts were ages >60. Eleven were male, and the majority (83%) were Caucasian. Twelve pts had early unfavorable disease (6 each with elevated ESR, B-symptoms, and bulky mediastinal masses). Eighteen pts had advanced stage disease (5 Stage 3, 13 Stage 4; IPS score 3 -4 in 7, 1-2 in 10). Adverse risk factors for all 30 pts included bulky disease or large mediastinal mass (n=12), B-symptoms (n=14) and extranodal disease (n=16). Overall therapy was well tolerated and most adverse events were grade 1-2. Related events of any grade included hypertension (n=10), rash (n=9), anemia (n=8), infusion reactions (n=5), elevated liver function tests (n=5), arthralgias (n=4) and hypo- or hyperthyroidism (n=3). Grade 3 and 4 events (whether or not judged to be related) were as follows Gr3: lymphopenia (n=4), febrile neutropenia (n=3), neutropenia (n=3), hypertension (n=2), diarrhea (n=1), hyperglycemia (n=1), and hyponatremia (n=1); Gr 4: neutropenia (n=10); transaminitis (n=1); sepsis (n=1). The only Grade 3 or 4 immune-related adverse event was the one grade 4 transaminitis that resolved with steroid administration and a delay in therapy. Eleven of 30 pts achieved CR (37%; Deauville 1-3) following initial PEM monotherapy including three with large mediastinal masses. Four additional patients with bulky disease and four others had major reductions in disease following PEM monotherapy, but did not achieve CR by Lugano criteria (Fig 1A). To better characterize the depth of response, we quantitated the decline in total metabolic tumor volume (TMV) (Fig 1B). Eight of the 17 pts with < CR to PEM monotherapy for whom TMV could be analyzed had > 90% reduction in TMV. A single pt had an atypical response with clearance of original disease sites, but development of new sites that resolved after two cycles of AVD. Across all pts, the CR (Deauville 1-3) rate following 2 cycles of AVD, was 100%. Median follow up is 6.5 (range: 1 - 12) months among those who have completed therapy. No pt has required a change in treatment, relapsed, or progressed, with progression-free and overall survival rates both at 100%. Conclusion: Although the study did not meet its primary endpoint, our data demonstrate that 3 cycles of PEM is highly active in pts with newly diagnosed early unfavorable or advanced stage cHL. PEM monotherapy resulted in > 90% reduction in TMV in the majority of pts, and when followed by AVD x's 2, CR in 100%. No pts have experienced progression or change of therapy to date and treatment was overall very well tolerated. This radiotherapy- and bleomycin-free approach warrants further investigation in larger trials to confirm response rates and assess efficacy compared with other novel combinations in the frontline setting. Disclosures Pro: Takeda: Consultancy, Honoraria, Other: Travel Expenses; Celgene: Consultancy, Honoraria; Kyowa Hakka Kirin: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Gordon:Gilead: Other: Advisory Board; Juno/Celgene: Other: Advisory Board, Research Funding; Zylem LLC: Other: co-founder; research in nanoparticles in cancer; Bayer: Other: Advisory Board. Winter:Merck: Consultancy, Research Funding.

Introduction Approximately 20% of patients (pts) with classical Hodgkin lymphoma (cHL) are age ≥ 60 years (yrs) at diagnosis (dx). Standard anthracycline-based therapies (ABTx) have historically shown lower efficacy and greater toxicity in this older population compared with younger pts, especially for unfit or frail pts. However, prior analyses have pre-dated the use of brentuximab vedotin (BV) and other novel targeted agents in the front-line setting and there remains no clearly defined or unified standard of care for this pt population. Studies in older lymphoma pts have also defined specific categories of pt fitness that may potentially guide therapy, although continued validation of these definitions in cHL are needed. We performed a large, multicenter retrospective study to identify current practice patterns in the US in older untreated cHL pts with specific attention to pt fitness using established definitions and to outcomes with ABTx versus non-ABTx. Methods Following IRB approval at each site, detailed pathologic and clinical data, including geriatric assessments (GAs) for the latter, were collected across 10 US academic medical centers. Eligible pts included: cHL dx on or after 1/1/2010, age ≥ 60 yrs at dx, and no preceding hematologic malignancy. Subjects with inadequate clinicopathologic and outcomes data or with dx other than cHL were excluded. A multivariable Cox proportional hazards model was developed to study the association of PFS and OS with various factors of interest, and survival rates were estimated by Kaplan-Meier using SPSS. Associations were considered significant for two-sided P values ≤ 0.05. Results Among 254 eligible older cHL pts with newly diagnosed disease, clinical features included: median age 67 yrs (range 60-90+), 54% male, 64% stage III/IV, 46% B symptoms, and 86.1% ECOG PS 0-1. 68.9% had nodular sclerosis, 18.9% mixed cellularity, and 12.2% other subtypes; EBV was detectable by IHC or peripheral blood in 39.3% of evaluable cases (n=98). In terms of geriatric measures, 31 pts (12.2%) had loss of at least one ADL; 40 (15.8%) had a geriatric syndrome; and 16 (6.3%) had both. Of note, only one pt underwent a comprehensive GA prior to treatment. Using established fitness definitions in lymphoma (Tucci et al, 2015), pts were classified as "Fit" (n=129; 50.8%), "Unfit" (n=8; 3.2%), or "Frail" (n=112 (44.1%); 5 (2%) were unclassifiable due to incomplete data (Table 1). Front-line regimens included ABVD (n=145; 57.1%), AVD (n=33; 13.0%), and CHOP (n=18; 7.1%). 6 pts (2.4%) received BV monotherapy; 21 (8.3%) received BV with AVD, the latter either concurrently (N=11) or sequentially (n=10). 11 pts did not receive systemic tx, of whom 9 received radiation alone; 58 pts received radiation with systemic tx. ABVD recipients received an average of 7.4 doses of bleomycin (range 1-14) and 18.4% (n=26) had pulmonary toxicity. In addition, 56.7% (n=130) of pts experienced at least one tx-related toxicity, which was similar across all fitness groups (Table 1). 15.1% (n=38) of pts stopped tx due to toxicity, which was noted more often in "frail" pts though it was relatively uncommon. 11 pts (4.3%) experienced treatment-related mortality (TRM). Compared with pts receiving non-ABTx, ABTx was associated with significantly improved PFS (HR 0.391, P=0.008) and OS (HR 0.195, P=0.0004). ECOG PS >1 was associated with inferior PFS (HR=1.96, P=0.017) and OS (HR=3.09, P=0.002). Pts defined as "frail" had no apparent difference in PFS compared with fit pts (Figure 1A;P=0.169), although decreased OS was seen (Figure 1B; P=0.01). Discussion To the best of our knowledge, these data represent one of the largest analyses of older cHL pts in the modern era. Our real-world analysis shows that in those who are able to receive them, anthracyclines provide meaningful survival benefit in this older cHL patient population and can be well-tolerated for many pts. The impact of dose intensity and backbone regimen are not yet known. In addition, current definitions of "fitness" incompletely identified pts at risk for poor outcomes or greater toxicity. Further studies are planned to better delineate fitness in this population. Disclosures Bartlett: Celgene: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Affimed: Research Funding; Merck: Research Funding; Janssen: Research Funding; Immune Design: Research Funding; Gilead: Research Funding; Millenium: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Forty Seven: Research Funding; Genenetech: Research Funding; Bristol-Myers Squibb: Research Funding. Grover:Seattle Genetics: Consultancy. Bennani:Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board. Hill:Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Advani:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Kura: Research Funding; Janssen: Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Regeneron: Research Funding; Infinity Pharma: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Agensys: Research Funding; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Cell Medica, Ltd: Consultancy; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Magarelli:Tevan Oncology: Speakers Bureau. Feldman:Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding. Cohen:Astra Zeneca: Research Funding; ASH: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Lymphoma Research Foundation: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Janssen Pharmaceuticals: Consultancy; Genentech, Inc.: Consultancy, Research Funding. Evens:Seattle Genetics: Consultancy, Honoraria, Research Funding; Tesaro: Research Funding; Epizyme: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria. Portell:AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding.

Introduction Platelets are transfused prophylactically to prevent hemorrhage in a variety of patient populations. However, guidelines indicate that prophylactic platelet transfusions in patients with platelet counts above 50k/uL are usually not indicated, with notable exceptions including those undergoing neurological or cardiac bypass surgery. Common minor procedures such as paracentesis, central line placement, and lumbar puncture have been safely performed at platelet counts below 50k/uL. Despite this evidence, our institution incurred approximately 10 million dollars (USD) in direct platelet costs in 2017, with nearly 40% of platelet transfusions are occurring when the patient's platelet count exceeded 50k/uL. Given the significant financial impact of, and potential adverse effects associated with inappropriate platelet transfusion, we implemented a best practice advisory (BPA) in our electronic medical record (EMR) in order to better characterize patterns of platelet transfusion orders in patients with platelet counts >50k/uL. Methods An EMR-embedded BPA was activated in the inpatient hospital setting of a large, tertiary care academic medical center on May 1, 2019, and triggered whenever a platelet transfusion order was placed on an admitted patient whose most recent documented platelet count was >50k/ul. To inform the comparative impact of BPA alerts on provider behavior, alerts were randomized at the patient level to trigger either in standard or silent fashion. For standard alerts, the BPA appeared on-screen, informing the provider that their platelet transfusion order was potentially inappropriate and citing supportive evidence. Providers had the option of following or overriding the alert (Figure 1). In case of alert override, a pre-specified or free text justification was requested. Pre-specified options included upcoming neurosurgery, cardiac bypass surgery, known qualitative platelet defects, or patients taking antiplatelet drugs. Charge data were based on charges for platelet transfusion orders as listed in the hospital charge master. Results From May 1, 2019 to July 30, 2019, the alert fired 181 times (Figure 2). Alerts were silently triggered in 64 (35%) cases. Of the 117 active alerts, 23 (20%) were followed and 94 (80%) were overridden. The most common reasons for alert override included prophylactic transfusions ahead of non-cardiac and non-neurosurgical operations (18%), upcoming cardiac bypass surgery (18%), qualitative platelet defects (12%), active central nervous system (CNS) bleeding (12%), and active non-CNS bleeding (7%). The estimated cost savings associated with followed alerts was $18,170 USD. Discussion Our BPA was effective in reducing instances of platelet transfusion orders by 20% over a three-month period, translating to an estimated annual savings of nearly $70,000 USD in hospital charges. Conversely, the 80% alert override rate indicates that platelet transfusion in patients with platelet counts >50k/uL remains common, occurring in a variety of contexts. Potentially appropriate reasons for platelet transfusions included orders in the setting of cardiovascular bypass surgery, active CNS bleeding, or qualitative platelet defects, representing circumstances in which platelet thresholds are often set higher than 50k/uL. Alternatively, 25% of alert overrides occurred in potentially inappropriate contexts, including patients undergoing non-cardiovascular/non-neurosurgical procedures and patients with non-CNS active bleeding, settings where routinely targeting a platelet threshold >50k/uL is not supported by evidence. As a result of our study's randomized design, future directions include comparative analyses between patient care encounters in which alerts were silently versus visibly triggered, allowing for rigorous determination as to whether providers' interaction with our BPA influences subsequent rates of potentially inappropriate platelet utilization as compared to a control group. Overall, our findings show that platelets are frequently ordered in potentially inappropriate settings, and that reducing these orders imparts significant financial savings. These results provide an impetus for interventions directed at educating providers on appropriate platelet ordering practices, in order to further reduce unnecessary expenditures and optimize patient care. Disclosures No relevant conflicts of interest to declare.

75 Background: Trust is an integral component of the physician-patient relationship, and its importance is magnified in oncology. In patients with uncommon cancers, aspects pertaining to the rarity of their diagnosis may further influence their inclination towards and perception of trust. We sought to delineate the existing literature landscape of trust in oncology and explore the meaning of trust for patients living with neuroendocrine tumors (NETs), a comparatively rare and chronic malignancy. Methods: We performed a MEDLINE search including combinations of the MeSH headings ‘trust’ and ‘neoplasms’, categorizing articles according to recurrent themes. These themes were then presented to a Northern California NET support group, followed by a discussion. Discussants’ narratives and lived experiences were evaluated with those captured by the current literature to assess areas of concordance as well as to identify areas in need of further study. Results: 355 articles were reviewed, of which 40 articles were included for analysis. Frequently cited factors contributing to measures of trust consisted of race discordance, empathic physician communication, and healthcare systems dynamics. Medical mistrust was associated with poorer cancer screening compliance, reduced adherence to therapy recommendations, and decreased quality of life. Support group participants’ perspectives affirmed these conclusions, adding the lack of medical community awareness of NETs as the major barrier to communicating with their physicians about symptom recognition and shared decision making. Conclusions: Trust in oncology is determined by factors related to patients, physicians, and the healthcare system in which they interact. Medical mistrust is associated with worse measures of cancer surveillance, treatment adherence, and quality of life. Patients with NETs uniquely implicated the insidious and rare nature of their disease, as well as lack of clinician expertise in community settings, in impairing communication with, and therefore, trust in their physicians. Efforts to improve physician-patient communication in those with rare malignancies are needed in order strengthen trust and optimize their care.

Introduction Thrombophilia diagnostics are frequently ordered in the inpatient hospital setting, but their impact on patient care is often equivocal. Thrombophilia testing is expensive, and many results are subject to confounding when ordered in the context of an acute hospitalization. Furthermore, these tests are frequently lost to follow-up or wastefully repeated after the patient is discharged. In this study, we conducted a retrospective chart review to determine the rate and financial impact of inappropriate thrombophilia test ordering across all inpatient services at Stanford Hospital over one calendar year. Methods Utilizing data from our finance department, we obtained a list of all inpatient thrombophilia testing ordered at Stanford Hospital from June 2014 through June 2015. Thrombophilia testing was defined as ordering any of the following: factor V Leiden, prothrombin G20210A mutation, antithrombin III, lupus anticoagulant, beta-2 glycoprotein 1 IgM/IgG, anticardiolipin IgM/IgG, dilute Russell viper venom time, protein C or protein S levels, and JAK2 V167F mutation. The criteria for defining a test as 'inappropriate' were guided by utilizing major society guidelines and current evidence, placing an emphasis upon the ordered tests' clinical relevance and reliability in the context of the patient's admission diagnosis. The criteria were formulated by a senior hematologist with specific expertise in thrombophilia evaluations. Two internal medicine resident physician data reviewers independently evaluated the ordered tests to determine their appropriateness. To ensure consistency between reviewers, identical test datasets were evaluated and compared, demonstrating satisfactory concordance (>0.85). When the appropriateness of a test was unclear, joint evaluation was performed with the entirety of the study team to arrive at a final conclusion. Each test was linked to the ordering primary service. Charge data for each individual test was obtained through our financial department. Aggregate data were evaluated manually. Results In total, we reviewed 889 individual orders involving 167 patients across 20 ordering specialties. Of the 889 total orders, 331 were deemed inappropriate (37.2%), translating into a cumulative hospital charge of $152,923 (Figure 1). The tests most frequently inappropriately ordered included antithrombin III (94.4%), factor V Leiden (93.2%), protein C (92.7%), protein S (92.2%), and the prothrombin G20210A mutation (89.3%). Ordering individual tests in the setting of clearly provoked thrombotic events, during the acute thrombotic period, while patients were on concurrent anticoagulation, or when results failed to impact management represented the most common reasons testing was deemed inappropriate. Ordering practices were then stratified across the hospital's different primary services. Of services with the highest volume of test ordering, General Medicine (38.1%) and Neurology (34.9%) ordered testing inappropriately at the highest rates, while Rheumatology (12.8%) and Hematology (15.9%) ordered inappropriately at the lowest rates. Notably, the non-teaching services ordered testing inappropriately at one of the highest rates (62.2%), though their volume of ordering was lower in comparison with the aforementioned groups. Discussion Our results illustrate the high prevalence and significant financial impact of inappropriate or unnecessary thrombophilia testing conducted in the inpatient setting at our institution. Factors confounding test validity were frequently present at the time of ordering. Furthermore, stratifying ordering practices by specialty illustrated the differential rates of inappropriate ordering between services. Even when thrombophilia testing results fail to impact short term decision-making, misappropriated labeling of patients as 'thrombophilic' can have a lasting negative impact on future anticoagulation decisions. Combined with the high cost of errant ordering, these serve as a strong impetus to reduce the rate of thrombophilia testing during inpatient hospitalizations. Our baseline data demonstrate a need for institution-wide changes such as implementing electronic best practice advisories or potential ordering restrictions, and of tantamount importance, service-specific educational interventions in order to reduce unnecessary expenditures and improve patient care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.