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Multifocal necrotizing leukoencephalopathy (MNL) is a rare condition typically described in patients undergoing chemotherapy or with HIV/AIDS. As a pathologic entity, it is characterized by multiple small foci of necrosis typically within white matter of the pons and occasionally in other areas. Herein we describe findings in 6 patients with MNL, 5 diagnosed at postmortem examination and 1 by surgical biopsy. Histopathologic features were characteristic, with generally small foci of necrosis, most frequently within the pontine base, although larger lesions were seen in the frontal white matter and basal ganglia. Axonal swellings, occasional dystrophic calcification and minimal microglial activity or reactive responses were common. Glial fibrillary acidic protein immunoreactivity was absent or markedly reduced within the lesions although it remained well defined in the surrounding areas. The underlying clinical circumstances ranged from HIV/AIDS, hematologic malignancy, chemotherapy for malignancies to postcardiac transplant, the latter reported for the first time. A significant common thread identified in our cases was altered immune status. A second common factor, which has also been previously implicated, was the presence of significant ongoing infection or sepsis. The role of concurrent inflammatory processes, specifically proinflammatory cytokine release in the context of these complex clinical scenarios is discussed with possible pathogenetic considerations.

Objective The main aim of this single-institution retrospective study was to elucidate the prognostic significance of CD30 expression in AITL. Methods We analyzed patients newly diagnosed with AITL at our institution between 2000 and 2020. Along with CD30 receptor testing, variables, including date of diagnosis, age, gender, stage, LDH level, platelets, hemoglobin, bone marrow involvement, and EBV receptor positivity, were collected. Treatment and progression data, including response to frontline therapy, presence of consolidation stem cell transplant (SCT), and usage of brentuximab-based treatment, were collected. Endpoints were progression-free survival (PFS) and OS. Univariate (UVA) and multivariate (MVA) Cox proportional hazard models were used to determine the significance of variables at diagnosis on PFS and OS. Results Out of the 295 individuals diagnosed with AITL, 129 patients with CD30 testing who had both response and survival data were included. This group had a median age of 65 (range 29–83) years and a male predominance (51%). Median follow-up time was 40 (range 2–137) months, with three-year PFS and OS of 48% and 23%, respectively. Sixty-seven individuals died within the first three years of the study. The 3-year OS is 46% in CD30+ individuals and 55% in those who are CD30– (p=0.578). PFS is 20% in CD30+ individuals and 29% in those who are CD30– (p=0.675). SCT (p=0.0003) was statistically associated with improved survival. For OS, age >65 (HR: 3.131, 95%CI: 1.545–6.344, p=0.0015), BM involvement (HR: 2.134, 95% CI: 1.151–3.956, p=0.0161), incomplete remission (HR: 2.208, 95% CI: 1–4.876, p=0.0499), male gender (HR: 0.367, 95% CI: 0.199–0.678, p=0.0014), no SCT (HR: 4.085, 95% CI: 2.119–7.872, p≤0.0001), and positive CD30 (HR: 0.322, 95% CI: 0.158–0.656, p=0.0018) were associated with inferior OS. Conclusion Age

e13067 Background: Recently, next generation sequencing (NGS) has been used with increasing frequency to guide therapy decisions for patients with metastatic solid tumors. NGS is a DNA sequencing technology that detects somatically acquired mutations. If an actionable mutation is identified, it may affect prognosis and guide therapy. At our institution we serve a large proportion of minority and underserved patients and analyzed their NGS results to determine if there was a change in management. Methods: Patients with metastatic breast cancer treated at one of two sites at Baylor College of Medicine who underwent NGS via Tempus between 2018-2020 were included. Tempus provided access to the variant database for these patients. We analyzed the charts of 43 patients who underwent NGS via Tempus on tissue, blood or both. In those patients with clinically actionable mutations, we noted if there was a change in management. Utilizing Redcap, we extracted demographics, sites of metastasis, biomarker activity and site, genomic sequencing, and duration and sequencing of therapies given along with clinical trial information. Results: Of the 43 patients included in this analysis, the mean age was 55 years, 33% were African American, 30% were Hispanic, 21% were white/non-Hispanic, 12% were Asian, 4% were other. Two thirds of patients were treated in the Harris Health System (a safety net hospital with a unique and diverse population) while one third was treated at the Baylor St. Luke’s Medical Center (a private academically affiliated institution). Of the 43 patients, 14 had PIK3CA mutations and 3 had a change in management. 2 patients had microsatellite instability (MSI) and received immunotherapy, and 1 patient had a HER2 mutation and entered a clinical trial with Neratinib. Additionally, 2 patients were incidentally found to have MUTYH germline mutation which is associated with polyposis. Conclusions: With increasing frequency, patients with metastatic malignancy undergo NGS in order to determine if there is an actionable mutation that can guide their next line of treatment. However, this technology could be cost prohibitive for many underserved patients. Our study analyzes a unique and diverse population of patients, many of whom are underserved. We were able conduct this testing in our cohort, study the frequency of somatic mutations and monitor for change in treatment. Of the variants analyzed, PIK3CA mutations are actionable and patients can receive Alpelisib + Fulvestrant- however many did not. There was not a large shift in management based on the incorporation of this DNA sequencing technology which suggests that, unlike the case of other solid tumors, there aren’t yet as many actionable targets for patients with metastatic breast cancer. Shared decision making along with consideration of cost is paramount for these patients as we shift into an era of highly personalized medicine.

10507 Background: In the recent decade, novel therapies have led to significant improvements in overall survival (OS) in symptomatic multiple myeloma (MM). With this increase in OS, there is an increase in the incidence of second primary malignancies (SPM) in patients with MM. This is related to multiple factors; we hypothesize that racial disparities also play a role. There is a paucity of studies with large, high quality datasets evaluating racial disparities in SPMs in MM. Our goal is to explore patterns of incidence of SPMs in US Veterans with MM, focusing on racial disparities. Methods: We conducted a retrospective cohort study based on electronic health record (EHR) and cancer registry data recorded in the VA’s Corporate Data Warehouse (CDW) between January 1, 1999 and January 1, 2018. We compared incidence of SPMs (defined as malignancies occurring after the diagnosis and treatment initiation of MM) using the standardized incidence rate ratio (IRR). Univariate and multivariable analyses were performed, using a Cox model adjusting for age, race, gender, treatment era, smoking status, and stage at MM diagnosis. Results: There were 8467 Veterans (97.4% male) with MM identified with self-reported race: White, 5029 (59.4%); AA, 2178 (25.7%); and other or unknown, 1260 (14.9%). At 7.5 years of follow up, 430 (5.1%) MM patients developed SPM while 8037 did not. 982 had received HSCT (Hematopoietic Stem cell transplant) of whom 65 (6.62%), a significantly higher proportion developed SPM versus those without HSCT (n = 7485) of whom 365 (4.87%) developed SPM (p = 0.024). Among those Veterans who had SPM 380 (88.3%) had solid tumors, 50 (11.6 %) had hematological malignancies. Of 88.3% with solid SPM the distribution was: prostate cancer, 113 (29.7%); digestive tract cancers, 63 (16.6%); lung cancer, 55 (14.4%); and GU (bladder/renal/testicular), 48(12.6%). The cumulative incidence of developing SPM increased steadily over time for the duration of this study period of 7.5 years from diagnosis. The median age of diagnosis for Whites was 68.2 years and for AA was 64.3 years, (p < 0.001) demonstrating that MM occurred earlier in AA. The hazard ratio for AA versus whites to develop SPMs was 1.21 (0.975-1.505) (p = 0.0823). However, the risk of prostate cancer was significantly higher in AA with an adjusted hazard ratio of 1.81 (1.196-2.739) (p = 0.005). No racial disparities were observed in the incidence of other types of SPMs. Conclusions: Our study suggests that the risk of SPMs does not plateau over a patient’s lifetime. HSCT was found to be an independent predictor of SPM, while smoking and agent orange were not. Our cohort is one of the largest groups of AA with MM in published literature. AA did not have a higher incidence of SPMs overall; but had a significantly higher incidence of prostate cancer than whites. We hope to develop an individualized predictive model for SPM in patients with MM.