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Introduction Indolent Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of diseases including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and follicular lymphoma (FL). These compose a heterogenous group of disorders that frequently measures survival in years due to the long natural history of these diseases. Frequency and morbidity of cardiac arrhythmias in patients with indolent lymphoma is unknown, but recent observations note that arrhythmias are an increasing problem. Due to advances in treatment for indolent NHL with emergence of novel therapeutics, combined with an aging population and a long natural history, understanding of arrhythmia burden in indolent lymphoma is an area of research with important implications for patients undergoing active treatment as well as for long term lymphoma survivors. Methods Adult patients 18 years or older with indolent NHL treated at the University of Rochester Wilmot Cancer Institute between 2013-2019 were included in the Cardio-Oncology Lymphoid Malignancies Database and analyzed. The primary objective of this study was to define the rate of arrhythmic events and sudden cardiac death in patients with indolent lymphoma during treatment. Cardiac arrhythmias including ventricular arrhythmias (VT/VF), atrial arrhythmias (atrial fibrillation (afib), flutter, SVT and atrial tachycardia), and bradyarrhythmias were identified using ICD-10 codes. Kaplan-Meier survival analysis was used to assess cumulative probability of arrhythmia. Results There were nine hundred and eighteen patients who were diagnosed with indolent lymphoma. Diagnoses included: CLL, N=414; FL, N=284; MZL, N=144; LPL, N=76. Median age was 64, and 43% were female. There were 383 (42%) patients who received treatment. Treatments were classified as chemotherapy, targeted therapy, monoclonal antibodies/immunotherapy, and combination therapy. There were no significant differences in baseline characteristics between treated and never treated patients. At the time of diagnosis, 277 patients (30%) had hypertension, 101 (11%) had prior history of arrhythmia. During median follow up of 24 months, 168 patients (18%) developed a new or recurrent arrhythmia based on ICD-10 codes documented in the electronic medical record. Sixty-three out of one hundred sixty-eight patients had both prior history of and recurrence of arrhythmia, while one hundred five had a new diagnosis of arrhythmia. Afib was the most common arrhythmia, noted in 81 patients (9%). At 6 months from diagnosis, cumulative probability of developing any arrhythmia was 8% (Figure 1). Of all arrhythmias, 89/168 (53%) occurred in SLL/CLL, 35/168 (21%) in FL, 17/168 (10%) in LPL, 27/168 (16%) in MZL. Arrhythmias on treatment occurred in 4/95 patients receiving chemotherapy alone (4.2%), 12/95 patients receiving monoclonal antibodies/immunotherapy (12.6%), and 28/95 patients receiving targeted therapy (29.4%). Most arrhythmias (51/95; 53.6%) occurred in patients receiving combination therapy (chemoimmunotherapy or targeted/immunotherapy). Overall, there were 80 (9%) deaths. Ten deaths were related to cardiovascular diseases; of which 8/10 (80%) were from sudden cardiac death. Conclusions This real-world cohort demonstrates that patients with indolent lymphoma could have an increased risk of cardiac arrhythmias that is increased by treatment. Afib was the most common arrhythmia identified in this study and appears increased compared to the incidence in the general age matched population (1-1.8 per 100 person-years). Surprisingly, of 80 deaths, 8 (10%) were attributed to sudden cardiac death. This data set contributes important information that can help identify patients at increased risk of cardiovascular morbidity and mortality that can impact treatment. Prospective monitoring in these patients may better define the incidence and associated risks of arrhythmias. Future directions will focus on risk factors for arrhythmias and developing an approach to prevent and treat arrhythmias in this patient population. Updated results will be presented at the meeting. Disclosures Zent: Acerta / Astra Zeneca: Research Funding; TG Therapeutics, Inc: Research Funding; Mentrik Biotech: Research Funding. Barr:Janssen: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Merck: Consultancy; Genentech: Consultancy. Reagan:Kite, a Gilead Company: Consultancy; Seattle Genetics: Research Funding; Curis: Consultancy. Friedberg:Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy.

Introduction Primary mediastinal large B cell lymphoma (PMBCL) is a rare non-Hodgkin lymphoma (NHL) with a female predominance; often presenting with a large anterior mediastinal mass. Though PMBCL has clinical and molecular features overlapping with Hodgkin lymphoma, it is a distinct entity defined by the World Health Organization classification. PMBCL is heterogeneously treated, and most patients receive front line therapy with either rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with radiotherapy (RT), or the more intensive etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with rituximab (EPOCH-R) regimen. Diagnosis of PMBCL is made using clinicopathologic criteria and radiographic imaging, however gene expression profiling (GEP) studies reveal a characteristic genotypic signature distinct from diffuse large B cell lymphoma (DLBCL). Molecular classification of PMBCL using the Lymph3Cx assay from formalin-fixed paraffin-embedded tissue (FFPE) is feasible, reproducible, and highly concordant in a training and validation cohort (Mottok et al. Blood 2018). Using a multicenter cohort of patients, we sought to estimate the rate of mis-match among patients with a clinical diagnosis of PMBCL using Lymph3Cx, and describe treatment selections and outcomes for each group. Methods Patients were identified from a cohort of patients with newly diagnosed NHL from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource, and the Lymphoma Epidemiology of Outcomes cohort. Patients were enrolled between 2002-2019, and included if they had clinically defined PMBCL. FFPE was retrieved from hematopathology archives of participating academic centers. All diagnoses of PMBCL were based on expert hematopathology review at the time of therapy, and all cases underwent classification by GEP using the Lymph3Cx assay. Lymph3Cx was performed in the clinical lab at the Mayo Clinic in Arizona: Contiguous unstained sections were deparaffinized and macrodissected to enrich for tumor content before RNA isolation;100-200 ng of total RNA was used in an nCounter Elements XT, hybridized, and processed the following day using the nCounter FLEX system. Raw counts were processed through the Lymph3Cx algorithm and results reported as probability of PMBCL (≥0.90 as PMBCL, ≤0.10 as DLBCL all other results "Unclear PMBCL/DLBCL") (A. Mottok et al, Blood, 2018). For cases classified as DLBCL, the Lymph2Cx cell-of-origin classifier results was reported (Scott et al, JCO, 2016). Time to event endpoints were described with Kaplan-Meier plots by groups defined by mismatch status and compared with a logrank test. Binary outcomes will be presented with 90% exact confidence intervals. Results Fifty patients were identified. Median age was 35 years (range 19-70). Sixty four percent were women. Median follow up was 47 months. Treatments included R-CHOP (44%), EPOCH-R (44%), and MACOP-B [methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin] (6%), other (4%). Ten patients (20%) had events (defined as progression or death). Three patients in the entire cohort (6%) died. The Kaplan-Meier estimated survival at 47 months (median follow-up) is 92%. The Lymph3Cx assay yielded gene expression data of sufficient quality in 47/50 cases (94%, 90% CI=85.2, 98.3%). Of 47 cases clinically identified as PMBCL, 5 unclear were DLBCL/PMBCL and 1 was Germinal Center B cell subtype of DLBCL. Among these 6 patients, 4 received R-EPOCH (66%), 1 received R-CHOP (16.6%). One patient had missing treatment data. One patient had an event requiring subsequent therapy; all patients remain alive. Conclusions Using 47 patients with PMBCL defined by histology, clinical and radiographic findings, and molecular features, we demonstrate high concordance between clinical phenotype and molecular genotype of PMBCL by Lymph3Cx. Among the 6 patients not classified as PMBCL, most received R-EPOCH. Differences in outcome by mis-match status await longer follow-up and further accrual of subjects to our data base. Our data suggest molecular genotyping may have a role in mediastinal presentations of large cell lymphoma to optimize treatment decision making. Disclosures Maurer: Nanostring: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding. Flowers:AbbVie: Consultancy, Research Funding; Kite: Research Funding; Burroughs Wellcome Fund: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; V Foundation: Research Funding; Bayer: Consultancy; National Cancer Institute: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Astellas: Consultancy; Bayer: Consultancy; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy; Roche: Other: Travel expenses; Seattle Genetics: Research Funding.

Background: 0.6% of the population is transgender or gender diverse (TGD) and have a gender that differs from their sex assigned at birth (Flores et al., Williams Institute, 2016). TGD people face mistreatment and discrimination, and represent a vulnerable population which is understudied and not well-captured in large cohorts (James et al., National Center for Transgender Equality, 2015). Thus, little is known regarding their cancer risks, prevalence, and outcomes, particularly in the realm of hematologic malignancies. Efforts to study malignancy prevalence in TGD populations are of utmost importance to improve patient care. Limited data suggests TGD patients have higher rates of certain cancers, including lymphoma, compared to other patients, but require validation (Braun et al., Epidemiol Rev, 2017). To accomplish this goal, we sought to design and implement a reproducible data collection strategy to identify TGD patients within a cohort of patients with lymphoproliferative disorders at the Wilmot Cancer Center. Methods: We reviewed the charts of 2200 unselected, consecutive patients with any lymphoproliferative disorder from a single-center, regionally representative, database at the University of Rochester. Our algorithm included searching the following variables for suggestion of TGD identity: demographics, preferred name/alias, medications, problem list, medical/surgical history, social history, an electronic medical record (EMR) lesbian, gay, bisexual, and transgender (LGBT) tab, and karyotype data if available. Additionally, we searched each chart for the following terms: "transgender," "trans," "transsexual," "gender," "genderqueer," "non-binary," "non-conforming," "male to female," "MTF," "female to male," "FTM," "male," and "female" to identify TGD patients. Data on diagnosis, treatment, and more detailed demographics were collected for patients identified as TGD. We report descriptive analyses of our results. Results: Three transgender patients with lymphoproliferative disorders were identified, comprising 0.1% of the database (95% CI 0%, 0.4%). All were white, transgender women with diagnoses of follicular lymphoma, chronic lymphocytic leukemia, and atypical angiotrophic t-cell infiltrate concerning for lymphomatoid papulosis. All three were identified by medication history and searches for the terms "female" and "transgender" as well as aliases differing from legal name. Conclusions: More oncologic research must be done to explore the prevalence of specific malignancies in TGD populations. Such research is limited by inconsistent documentation of gender identity in EMRs resulting in lack of basic epidemiologic data on TGD people with cancer. Our chart review successfully identified three transgender patients. Among the methods used, medication histories, discrepancies between legal name and alias, and searches for the words "transgender" and "female" provided the most fruitful results. We expected diagnoses related to transgender identity, documentation of transgender identity, and the LGBT tab to yield significant results. However, these were low-yield sources in our study. Our inability to identify a percentage of TGD patients similar to prior data was likely multifactorial: 1) TGD patients may not want their gender identities known to oncologists and may not share related information; 2) oncologists may not ask about gender identity or related histories; and/or 3) TGD patients may seek care at outside institutions. Alternatively, the prevalence of lymphoma may be low in TGD populations, conflicting with prior data. Further research regarding TGD patients with hematologic malignancies necessitates specific collection of gender identity data within the EMR and large datasets such as the cooperative groups. More research is needed regarding the optimum questions regarding gender identity which will yield accurate data and maintain strong relationships between patients and providers. Disclosures Casulo: Celgene: Research Funding; Gilead: Honoraria, Other: Travel, accommodation, expenses; Roche: Other: Travel, accommodation, expenses.