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Venetoclax, a highly selective Bcl-2 inhibitor, is an orally bioavailable drug that has been approved as first-line therapy for chronic lymphocytic leukemia (CLL) in combination with obinutuzumab, as well as monotherapy in the setting of relapsed CLL. Although some of its life-threatening side effects are well known, including tumor lysis syndrome and cytopenias, others less known side effects include skin reactions. Skin rash is commonly reported in literature, which is often mild and not life-threatening. In this case report, the authors describe what is potentially the second case of venetoclax-induced vitiligo reported in literature. A 77-year-old man with CLL Rai stage II with cytogenetics showed 11 q23 deletion in 14% of cells, and 14q32 partial deletion in 9% of cells developed vitiligo in his extremities 2 years into treatment. A decision was made to continue venetoclax with close monitoring as the side effect was mild and not debilitating. The patient continued to do well. Although vitiligo is not associated with increased mortality risk, its development is associated with increased psychological stress. The mechanism by which vitiligo develops remains unclear. There may be an association between drug-induced vitiligo and improved cancer prognosis; however, larger studies need to be carried out to prove this hypothesis.

Primary breast lymphoma (PBL) is managed differently among centers, using surgery, systemic therapy and/or radiation. With data derived from the National Cancer Database (NCDB), we aim to describe treatments utilized in the United States, estimate the overall survival (OS) of different therapeutic modalities and determine the role of systemic therapy in patients with PBL.We conducted a retrospective cohort study using de-identified data from the NCDB. The NCDB provided records of 4616 patients diagnosed with PBL between 2004 and 2015. We excluded patients diagnosed with HIV, with no survival data, not treated in the reporting facility, without histologic confirmation, with stage III/ IV disease and for whom surgery, radiation, or systemic therapy was contraindicated. Both propensity score weighting and Cox models were used to obtain adjusted estimates. Based on histopathology, PBL was classified into indolent (I-PBL) and aggressive (A-PBL).In a sample size of 2063 PBL patients, the median age was 67 years (interquartile range (IQR): 57-78), and 97% were females. In 1027 patients with I-PBL, the median follow-up was 66 months (95% confidence interval (CI): 32.6-107.2) and 60% of patients had extranodal marginal zone subtype. Systemic therapy did not improve adjusted-OS (median: 154 vs. 143 months, P = 0.36) (Hazard ratio (HR): 0.86, 95% CI: 0.60-1.25, P = 0.42). The treatment arms associated with the highest adjusted 5-year OS were as follows: radiation (85%), surgery (79%), systemicradiation (87%) and radiationsurgery (87%) (P = 0.9). In 1036 patients with A-PBL, the median follow-up was 67.4 months (95% CI: 35.9-105), and 87% of patients had diffuse large B-cell subtype. Patients with A-PBL who received systemic therapy had an improved adjusted-OS (median: 115 vs. 72 months, P 0.01) (HR: 0.45, 95% CI: 0.38-0.53, P 0.001). The treatment arms associated with the highest adjusted 5-year OS were: systemic (69%), systemicradiation (77%), systemicradiationsurgery (79%) and systemicsurgery (79%) (P = 0.4).Systemic therapy used as first-line treatment is essential in A-PBL. Local therapy in the I-PBL using surgery and/or radiation is effective in long-term disease control. There is significant variation in front-line treatment modalities utilized in PBL across the US, many associated with similar outcomes.

The addition of radiation to chemotherapy in elderly patients with primary central nervous system lymphoma (PCNSL) remains controversial. This aim of this study was to assess the trend of combined modality treatment (CMT) and compare its survival with chemotherapy alone and radiation alone in non-HIV patients.We identified 6,537 patients who received single treatment modality, CMT, or no treatment at all between 2004 and 2015 from the National Cancer Database. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of CMT use. A propensity score weighting methodology was used to compare survival outcomes.Only 12.8% of patients received CMT, and this proportion steadily declined between 2004 (17.7%) and 2015 (8.7%), with an APC of -6.0% (95%CI=-8.0 - -4.0, p-value0.001) during the 12 years. Apart from classical prognostic factors (age and comorbidities), treatment selection was significantly influenced by sex, facility type, degree of urbanization, and type of insurance. CMT had improved survival [median overall survival 19.5 months (95%CI=15.7-22.8)] compared with single-modality treatment. This effect was more prominent in the first year.Socioeconomic factors affect the selection of treatment in elderly patients with PCNSL. CMT is falling out of favor in this patient population due to the risks of neurotoxicity. Further work should focus on developing strategies that minimize toxicity and access disparities without compromising survival.

Primary CNS lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal cord in the absence of systemic disease. Primary dural lymphoma (PDL) arises from the dura mater of the brain. It differs biologically from other CNS lymphomas. It is usually a low-grade B-cell marginal zone lymphoma (MZL), whereas other types of PCNSL are usually high-grade large B-cell lymphoma. This specific pathological subtype has important therapeutic and prognostic implications, making PDL a distinct subtype of PCNSL. Herein, we report a case of PDL in an African American patient who presented with chronic headaches. MRI of the brain showed a dural-based homogeneously enhancing extra-axial mass along the left hemisphere and was contained within the anterior and parietal dural matter. The malignant cells stained diffusely positive for CD19, CD20, and CD22 but negative for CD5, CD10, Cyclin D1, and CD56. Ki67 was 10–20%, consistent with extranodal marginal zone lymphoma. Given the location and pathology, the patient was diagnosed with PDL. She was started on treatment with bendamustine and rituximab. Due to Marginal Zone Lymphoma’s indolent nature, location outside the blood brain barrier, and known efficacy of bendamustine-rituximab, we decided to treat our patient with Bendamustine-Rituxumab. She completed six cycles, and post-therapy MRI brain showed complete remission. Our case adds to the sparse literature about primary dural lymphoma.

Oral manifestations of side effects of medications, such as methotrexate (MTX) for management of rheumatoid arthritis (RA) and mycophenolate mofetil (MMF) for solid organ transplant (SOT), are very rare. The known side effects include entities called other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) due to immunosuppression caused by these medications. While there has been an increased incidence of oral cavity LPD reported in the literature associated with MTX, oral presentations that involve MMF are rare. This case report will detail a 74-year-old man with scleroderma treated with MMF who developed Epstein-Barr virus + polymorphic B-cell lymphoproliferative disorder in the right maxillary gingiva presenting as osteonecrosis of the jaw (ONJ). His oral presentation was successfully treated with a combination of surgery and MMF dosage reduction with an oral presentation free of disease at 6 months follow-up. This is the first known case report of an oral manifestation of MMF-related OIIA-LPD.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of various B-cell malignancies. However, it can cause serious adverse effects like immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS is attributed to disruption of the blood-brain barrier due to inflammatory cytokines and increased levels of immune effector cells (IECs) in the cerebrospinal fluid (CSF). Corticosteroids and supportive management are the mainstays of ICANS treatment. However, no guidelines exist for the treatment of steroid-refractory ICANS. Some reports have shown favorable outcomes with no long-term complications in patients with steroid-refractory ICANS treated with intrathecal (IT) chemotherapy.We describe the outcomes of two patients with steroid-refractory ICANS treated with IT chemotherapy. Both patients had refractory large B-cell lymphoma and were not candidates for autologous transplant. They developed steroid-refractory ICANS after CAR T-cell infusion. IT chemotherapy with 12 mg methotrexate and 50 mg hydrocortisone resulted in prompt neurological improvement in both patients. One of them passed away due to multiple other comorbidities, and the other patient continues to do well without any complications.IT chemotherapy could be considered as a potential approach for the management of steroid-refractory ICANS based on our experience. Prospective studies are needed to validate this approach.

A minority of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergo surgery before the initiation of systemic therapy. The aim of this study is to explore the characteristics of patients undergoing surgery prior to systemic therapy (surgfirst), the predictors for surgfirst, and the survival outcomes.The National Cancer Database was queried for patients with DLBCL diagnosed between 2006 and 2015, and we performed a subgroup analysis of patients that received surgfirst. Time-to-initial therapy (TTI) was defined as the time in days (d) from diagnosis to systemic therapy. Overall survival was measured from the day of diagnosis in terms of months (m).Factors associated with lower likelihood of surgfirst were non-Hispanic Black race (p-value0.005), rural location (p-value0.005), treatment at academic center (p-value0.005), Medicaid insurance (p-value=0.01), comorbidity score=3 (p-value 0.007), year of diagnosis, advanced stages of disease, and presence of B-symptoms. The TTI of systemic therapy was delayed in the surgfirst group - 34 (IQR 22-52) days vs. 23 (IQR 13-38) days, p-value0.005. The five-year overall survival was 62.7% (95% CI 62.1-63.2%) vs. 58.3% (95% CI 57.7-60.0%) - HR 0.87 (95% CI 0.85-0.89), p-value0.005. The factors associated with higher mortality were advanced comorbidities, lower educational status, disease primarily located in the bone, brain, and spinal cord, advanced clinical stage, presence of B-symptoms, and advanced age.Despite the delay in systemic therapy, we could not identify a detrimental impact of surgfirst on survival. This needs to be confirmed in large-scale multicenter studies. We identified clinical and socioeconomic factors that affect treatment selection and survival.

Human immunodeficiency virus (HIV) infection may be a predictor of undertreatment of patients with lymphoma. We hypothesized treatment with systemic therapy (SysT) or hematopoietic stem cell transplantation (HCT) in the first-line setting leads to improved outcomes and sought to compare the predictors for treatment and outcomes with non-HIV (HIV-) patients.Patients with lymphoma diagnosed between 2004 and 2015 were extracted from the National Cancer Database (NCDB). Patients were categorized as HIV+ and HIV-. First-line treatment was categorized as no systemic therapy reported (noSyst), SysT, or HCT. Multivariate analysis to predict treatment and survival was performed.We identified 552,513 lymphoma patients, of whom 11,160 HIV+ versus 349,607 HIV- patients were eligible for analysis. Among HIV+, the positive predictors for SysT were insurance and higher income, whereas female sex and minority racial status predicted lower likelihood for SysT. Forty HIV+ patients underwent HCT. Treatment of HIV+ lymphoma patients resulted in improved outcomes: 3-year overall survival 43.6% in noSyst versus 58.1% SysT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.52-0.61; P .005) versus 62.2% HCT (HR 0.42; 95% CI, 0.14-1.3; P = .08). The outcomes were lower compared to non-HIV patients (3-yr overall survival 67.3% with SysT and 62.2% HCT).Patients with lymphoma with HIV benefit from SysT when feasible but outcomes are worse than non-HIV patients. HCT should be offered to HIV+ patients with lymphoma in the appropriate clinic setting. Individual characteristics of the patients and complications could not be evaluated in the present study but should be a focus for future research.

Introduction Multiple myeloma (MM) is the second most common hematological malignancy, accounting for 1% of all cancers, with median age of diagnosis between 66–70 years. MM remains incurable despite advances in treatment over time. Lenalidomide is an important medication used in induction therapy for MM and is also used for maintenance therapy for standard risk patients. With its increasing use, data is emerging about its use being associated with increased risk of secondary primary malignancies (SPM), especially when used as maintenance therapy. Case series: In this case series, we describe three patients with refractory MM treated with lenalidomide maintenance who later developed sALL. All had a common presentation of pancytopenia. They developed cytopenias while being on lenalidomide which was refractory to lenalidomide cessation, prompting bone marrow biopsy. Management and outcome: Lenalidomide was subsequently stopped, and patients were treated for secondary B-ALL. However, all passed away either due to relapse of disease or complications arising from treatment. Discussion: The mechanism of lenalidomide associated SPMs is not well understood however its incidence is well documented. At least 13 cases of ALL (predominantly B-cell ALL) following Immunomodulator imide drugs (IMiDs) have been reported in literature. An analysis of a larger cohort of patients is required to determine causality of lenalidomide with sALL. However, benefits of maintenance lenalidomide in patients with MM outweighs the risk of developing SPMs. Albeit persistent pancytopenia on lenalidomide therapy should be evaluated with bone marrow biopsy since it could be caused by secondary B -cell ALL.

The best consolidation strategy after induction chemotherapy in Primary CNS Lymphoma (PCNSL) remains controversial. Our objective is to estimate the overall survival (OS) for autologous stem cell transplantation (ASCT) versus whole brain radiation (WBRT) in the consolidation setting. We also sought to evaluate the factors affecting treatment selection METHODS: We identified 1620 patients with PCNSL who received chemotherapy followed by either ASCT or WBRT between 2004 and 2015 from the National Cancer Database. A propensity score weighting methodology was used to compare survival outcomes. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of ASCT use.Only 12.2% of patients received ASCT, and this proportion rose steadily between 2004 and 2015, with APC of +23%. Treatment selection was affected by age, type of area, distance from the treating facility, and level of education. With a median follow-up of 68.4 months, adjusted-median OS was 91.4 months and not reached for WBRT and ASCT groups, respectively (P.001). 5-year OS was 74.4% in the ASCT group versus 58.7% in the WBRT group (HR 0.40, 95% CI 0.27-0.60, P -value.01).Socioeconomic factors affect the selection of consolidative treatment in patients with PCNSL which can alter outcomes. Frequency of consolidative ASCT is increasing for patients with PCNSL. This is the first and largest cohort study, to our knowledge, to show an OS advantage in favor of ASCT. This OS benefit needs to be confirmed in a randomized controlled fashion.

Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have demonstrated the safe and efficacious use of fibrinogen replacement therapy (FRT) as a therapeutic approach to prevent hemorrhage and fetal loss in pregnant women with CD. In this case report, we present a 28‐year‐old pregnant woman who sought testing for CD given her family history. She denied any current or previous bleeding symptoms. Laboratory testing confirmed the diagnosis of CD. She was treated with FRT and prophylactic anticoagulation starting in her third trimester. She had preterm labor that prompted an urgent cesarean section with FRT support. This case adds to the sparse literature about fibrinogen disorders in pregnancy, and highlights the benefits, safety, and tolerability of FRT and prophylactic anticoagulation in pregnant women with CD. Finally, it emphasizes the importance of a multidisciplinary team approach for an uneventful delivery.

Background The American Society of Clinical Oncology recommends that patients with advanced cancer receive palliative care services in concurrence with active treatment. While the benefits of palliative care are clear, integration of palliative care can be challenging. We aim to review rates of palliative care consultation in patients with advanced pancreatic cancer at our institution, intending to improve these rates. Methods We retrospectively reviewed the electronic records of all patients with pancreatic cancer treated at Allegheny General Hospital diagnosed between 2009-2020. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Results Of the 171 patients reviewed, 121 completed all treatment and evaluation within our health network (Pittsburgh, United States). The median age was 63 years (IQR 40-91 years); 55 patients (45%) were male; the majority were white (107 patients, 88%). At the time of diagnosis, 28% of our patients had stage IV disease (34 patients), and 19.8% of patients who developed stage IV disease had palliative care referrals. Conclusions Palliative care is an integral part of usual care for advanced pancreatic cancer. Our analysis showed that palliative care is underutilized in our hospital. We aim to improve palliative care integration in our patients’ care by adding a hard stop to electronic medical records to remind physicians to offer palliative care to our patients with pancreatic cancer and to arrange lecture series to emphasize the importance of palliative care in this setting.

BackgroundThe addition of radiation to chemotherapy in elderly patients with PCNSL remains controversial. Our objective was to assess the trend of combined modality treatment (CMT) and compare its survival with chemotherapy alone and radiation alone in non-HIV patients. MethodsWe identified 6,537 patients who received single treatment modality, combined modality treatment, or no treatment at all between 2004 and 2015 from the National Cancer Database. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of CMT use. A propensity score weighting methodology was used to compare survival outcomes. FindingsOnly 12.8% of patients received CMT, and this proportion steadily declined between 2004 (17.7%) and 2015 (8.7%), with APC of -6.0% (95% CI -8.0 to -4.0, p-value Conclusion Socioeconomic factors affect the selection of treatment in elderly patients with PCNSL that can alter outcomes. CMT is falling out of favor in this patient population due to the risks of neurotoxicity. Further work should focus on developing strategies that minimize toxicity and access disparities without compromising survival

Extramedullary plasmacytoma (EMP) is a plasma cell disorder involving soft tissues in the absence of clonal bone marrow involvement or destructive bone lesions. When present in the gastrointestinal (GI) tract, and specifically the small intestine, it can cause a wide range of symptoms including GI bleeding, obstruction, and abdominal pain. The diagnosis is challenging, as it can hold an indolent course, and is infrequently encountered in clinical practice. Diagnosis requires biopsy of the involved organ, which can be obtained during surgery or endoscopy, and other workup to rule out systemic disease and bone marrow involvement. Treatment depends on the primary site of disease involvement and the presence of other features of systemic disease. We report a case of multiple small bowel plasmacytomas in a 51-year-old female who presented with small bowel obstruction. She eventually underwent surgical resection and is currently on chemotherapy awaiting stem cell transplant.

Chemotherapy use in the last month of life is an indicator of poor quality of end-of-life care.We assessed the frequency of chemotherapy use at the end of life at our comprehensive cancer center in Jordan and identified the factors associated with chemotherapy use.We conducted a retrospective chart review to examine the use of chemotherapy in the last 30 days and 14 days of life in consecutive adult patients with cancer seen at King Hussein Cancer Center (KHCC) who died between January 1, 2010, and December 31, 2012. We collected data on patient and disease characteristics, palliative care referral, and end-of-life care outcome indicators.Among the 1714 decedents, 310 (18.1%) had chemotherapy use in the last 30 days and 142 (8.3%) in the last 14 days of life. Over half (910; 53.1%) had a palliative care referral. Chemotherapy use in the last 30 and 14 days of life were associated with younger age (odds ratio [OR] 0.99/yr, P = 0.01, and OR 0.99/yr, P = 0.01, respectively) and hematological malignances (OR 1.98, P 0.001, and OR 2.85, P 0.001, respectively). Palliative care referral was significantly associated with decreased use of chemotherapy in the last 30 (OR 0.30, P 0.001) and 14 (OR 0.15, P 0.001) days of life.A sizable minority of patients with cancer at KHCC received chemotherapy at the end of life. Younger patients and those with hematological malignancies were more likely to receive chemotherapy, whereas those referred to palliative care were significantly less likely to receive chemotherapy at the end of life.

e21053 Background: Treatment with immune checkpoint inhibitors (CPI) targeting PD-1 or PD-L1 significantly improves progression free survival and overall survival in patients with non-small cell lung cancer (NSCLC). Emerging literature suggests that the proinflammatory state of CPIs may increase the risk of thromboembolism, both venous (VTE) and arterial (ATE), which is of great concern as thromboembolism remains a major cause of mortality in patients with NSCLC. We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients on immunotherapy for NSCLC. Methods: We reviewed the records of all patients diagnosed with stage IV NSCLC between December 2016 and December 2019 and treated with chemotherapy, CPIs, or both in one of the largest integrated academic health systems in Western Pennsylvania. Khorana scores (to predict the risk of future VTE) were calculated for each patient based on available data at the time of diagnosis. Logistic regression analyses were done to evaluate clinical predictors of VTE. Survival outcomes were analyzed using Kaplan-Meier estimates and a log rank test was used to compare survival estimates. Data was analyzed using SPSS v26 (IBM Corp). Results: A total of 110 patients with stage IV NSCLC were identified, 87.1% had ECOG ≤2, 67.0% had adenocarcinoma and 25.7% had squamous cell carcinoma, and 39.1% had PD-L1 staining ≥50%. Immunotherapy related adverse events (IrAE) of any grade were found in 28.2%. Overall, 25.5% received chemotherapy only, 27.7% received CPIs alone, and 45.5% received chemo + CPIs. A Khorana score of ≥2 was found in 43.6% of patients. Prophylactic anticoagulation was used in 0.9% of patients. VTE was detected in 18.3% and ATE in 10.0% of the cohort; therapeutic anticoagulation was given in 14.7% of patients. Median overall survival was 25.5 months (95% CI 18.7-32.3) in patients without VTE versus 13.7 months (95% CI 3.1-24.3) in patients with a VTE diagnosis (HR 1.96, 95% CI 1.11-3.45; p = 0.02). Khorana score of ≥2 was not a significant predictor of VTE in this cohort (univariate OR 1.34, p = 0.53, multivariate OR 1.13, p = 0.81), but was associated with worse survival (HR 2.38, 95% CI 1.48-3.83, p < 0.001). Conclusions: In this retrospective cohort, VTE was associated with decreased overall survival. While no significant association between elevated Khorana score and VTE was identified, elevated Khorana score at the time of diagnosis was an independent predictor of survival in patients with NSCLC. Of note, there was a low rate of prophylactic anticoagulation in this cohort.

e19021 Background: Blinatumomab, a bispecific (CD3/CD19) T-cell engager, is indicated for the treatment of acute lymphoblastic leukemia (ALL). The initial portion of each cycle is administered in the inpatient setting for close monitoring for cytokine release syndrome and neurotoxicity. Real world data are lacking on the cost of hospitalization, length of stay (LOS), and mortality in inpatients treated with blinatumomab. The goal of this study was to analyze the clinical outcomes of inpatient blinatumomab administration utilizing a national database. Methods: The ICD-10 diagnosis and procedure codes were used to identify Blinatumomab admissions and related complications from the 2018 version of the Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP). Weighted analysis was used to calculate national estimates. Logistic regression analyses were used to examine predictors of hospital outcomes (in-hospital mortality, length of stay, and cost), with p < 0.05 considered statistically significant. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results: A total of 228 patients received inpatient blinatumomab in this cohort. Median age was 46 years old (IQR 26.8, 63.0) and 59.2% were males, 50.4% were white, and 47.4% had private insurance. The majority of patients received care at an urban teaching (96.1%) or large hospital (76.3%). The most relevant inpatient complications during hospitalization included hypotension (7.5%), pneumonia (6.1%), sepsis (9.2%), seizure (2.2%), neutropenia (6.1%), thrombocytopenia (14.0), tumor lysis syndrome (3.9%), and acute kidney injury (9.6%). Median LOS was 9.0 days (IQR 3.0-16.2) and median hospitalization charge was $114,936 USD (IQR 51,984.2-240,557.5). On multivariate regression analysis, dialysis (OR 1.67, 95% CI 1.05-2.65), blood product transfusion (OR 1.5, 95% CI 1.14-1.97), sepsis (OR 2.63, 95% CI 1.86-3.73), neutropenia (OR 1.86, 95% CI 1.23-2.81), and pancreatitis (OR 1.46, 95% CI 1.11-1.91) were all associated with longer LOS. Dialysis (OR 1.83, 95% CI 1.29-2.6), transfusions (OR 1.52, 95% CI 1.01-2.28), sepsis (OR 1.87, 95% CI 1.20-2.91) and neutropenia (OR 1.84, 95% 1.04-3.24) significantly increased the cost of hospitalization. Conclusions: In this cross-sectional study of a large national cohort of patients receiving inpatient blinatumomab, multiple blinatumomab associated toxicities led to increased LOS and cost of hospitalization.

e19501 Background: Chimeric antigen receptor T-cell therapies (CAR-T) improve relapse free survival and durable remission rates in patients with relapsed/refractory large B-cell lymphoma (LBCL) and received US FDA approval in 2017. The cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity (ICANS) due to CAR-T cell therapy require close inpatient monitoring. Real world data are lacking regarding the cost of hospitalization, length of stay (LOS), toxicity, and mortality associated with CAR-T. The goal of this study was to analyze the clinical outcomes of inpatient CAR-T utilizing a national database. Methods: Data was collected from the 2018 version of the Nationwide Inpatient Sample (NIS) database. Patients who received CAR-T were identified with ICD-10 disease and procedure codes . Complex weights were used to enable appropriate national projections. The association between toxicity (particularly related to CRS and ICANS) and outcomes was examined using logistic regression analyses (p < 0.05 statistically significant). SAS v9.4 (SAS Institute, Cary, NC) was used for data analysis. Results: 306 patients met selection criteria. Demographic criteria were as follows: 61.1% males, 62.4% white, median age 58.0 years old (IQR 45.2-65.0), and private insurance (56.9%). A majority received care at urban teaching (97.7%) and large hospitals (73.2%). Relevant complications during hospitalization included hypotension (24.5%), pneumonia (8.5%), sepsis (9.8%), seizure (5.9%), neutropenia (24.5%), thrombocytopenia (8.8%), tumor lysis syndrome (TLS) (3.3%), and acute kidney injury (AKI) (14.1%). Median LOS was 16 days (IQR 12.0-22.0), median charge for hospitalization was $493,887 USD (IQR 143,400.0-1,182,940.0), and inpatient mortality was 5.2%. On multivariate regression analysis, inpatient mortality was significantly higher in those with intubation (OR 30.1, 95%CI 3.45-262), sepsis (OR 9.49, 95%CI 1.48-60.7), TLS (OR 18.9, 95%CI 2.52-140), AKI (OR 24.7, 95% CI 1.37-447) and thrombocytopenia (OR 53.4, 95% CI 2.19-1,298). LOS was higher in those with blood transfusion (OR 1.29, 95% CI 1.08-1.53), sepsis (OR 2.04, 95% CI 1.59-2.61), pancreatitis (OR 2.03, 95% CI 1.09-3.77), pneumonia (OR 1.39, 95%CI 1.04-1.87) and treatment in urban teaching hospitals (OR 1.53, 95%CI 1.02-2.30). Increased hospitalization charges were associated with hypotension (OR 1.54, 95%CI 1.14-2.08) and with treatment at urban teaching hospitals (OR 7.46, 95%CI 4.67-11.9) and medium size hospitals (OR 1.49, 95%CI 1.04-2.15). Conclusions: Inpatient mortality, median LOS, and hospitalization charges in inpatients treated with CAR-T can be significantly increased not only by inpatient complications, but also by the size and type of the treating facility. These findings highlight the financial burden of CAR-T cell therapy in the real world and can be used to shape future healthcare policy.

e18683 Background: Cancer-directed therapy, including cytotoxic chemotherapy and immunotherapy, is a known risk factor for decreased SARS-CoV-2 seroconversion after vaccination, as a result of impaired viral immunity. Outcomes of COVID-19 infection are worse in patients on active treatment, especially those with hematologic malignancies or undergoing stem cell transplantation. The association between cancer subtypes and seroconversion rates is not well established. The goal of this study was to investigate predictive factors for SARS CoV-2 seroconversion and infection. Methods: We reviewed the electronic medical records of all patients with documented SARS CoV-2 antibody levels (between 7/2020-8/2021) in one of the largest integrated health systems in Pennsylvania. Patients who had a diagnosis of hematologic or solid malignancy, were on active treatment (including adjuvant), and had received ≥1 dose of an FDA authorized SARS CoV-2 vaccine were included. Data regarding SARS CoV-2 serology, vaccination, cancer history, and treatment regimens for each patient were collected systematically. Positive serology (reflecting seroconversion) was defined as any value ≥0.8 units/mL. Logistic regression analyses were used to examine predictors of seroconversion. Data was analyzed using SPSS v26 (IBM Corp). Results: A total of 292 patients met the inclusion criteria. Hematologic malignancy was present in 80.5% of the patients and solid tumors in 26.7%. Active disease was present in 71.6% of the cohort. Two vaccine doses were given to 92.5% of the patients and 54.8% of patients received a booster dose (95.2% received mRNA vaccines, either BNT162b2 (Pfizer BioNTech) or mRNA-1273 (Moderna)). A history of COVID-19 infection was present in 15.1% of patients, 59.1% of whom were seropositive. Rates of seroconversion were equivalent in those who received the BNT162b2 (70.2%) or mRNA-1273 (70.9%) vaccines. Seroconversion rates were 69.9% in those with active disease, 81.9% without evidence of disease, and varied by diagnosis as follows (indolent B-cell lymphoma 73.3%, aggressive B-cell lymphoma (BCL) 55.9%, plasma cell dyscrasia 80.1%, CLL 39.5%, myeloid disorder 90.2%, lung cancer 80%, breast cancer 80%, GI cancers 81.3%, and GU cancers 76.9%). On univariate regression, receipt of treatment for CLL (OR 5.79, 95% CI 2.92-11.48, p < 0.001) and aggressive BCL (OR 2.44, 95% CI 1.17-5.09) were predictive of negative serology. Results were not changed on multivariate regression when adjusted for age and active treatment. Conclusions: In this retrospective cohort of vaccinated patients on cancer-directed therapy, treatment for aggressive BCL and CLL was associated with negative seroconversion. In addition, more breakthrough infections occurred in seropositive patients, suggestive of underlying immunodeficiency related to treatment or decreased vaccine efficacy despite formation of virus-specific antibodies.

e16229 Background: Obesity has been associated with decreased survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, exact reasons remain unclear. Reduced response to chemotherapy because of obesity-induced desmoplasia has been proposed as a mechanism for the suboptimal response to treatment and therefore worse outcome. To this end, we attempted to determine the effect of obesity on the efficacy of neoadjuvant chemotherapy in patients with resectable and potentially resectable PDAC who underwent surgical resection. We assessed rates of microscopic tumor-free margins as a surrogate for treatment response. Methods: We performed a retrospective review of all patients diagnosed with PDAC from 2017-2019 at Allegheny Health Network. Obesity was defined as BMI > 30 kg/m2. Patients with resectable and potentially resectable disease who eventually received surgical treatment were included.Demographics, treatment details, and surgical pathology results were reviewed. Two-sided Mann-Whitney U test and Fischer’s exact test were used to evaluate differences between groups with continuous and categorical variables, respectively. A p value of < 0.05 was considered as level of significance. Results: Out of 121 patients who received and completed treatment at our institution, 29 patients underwent neoadjuvant chemotherapy followed by surgical resection. Most patients were female (61%), Caucasians (90%), had stage I (76%) and potentially resectable disease (72%). Eleven (38%) patients were categorized as obese and remaining non-obese. Among patients who underwent surgery after neoadjuvant chemotherapy, 10 out of 11 patients (90.9%) had microscopic tumor-free margins in the obese group when compared to 17 out of 18 patients (94.4%) in the non-obese group. (Table). Conclusions: Our study revealed no significant difference in obese patients compared to non-obese patients in terms of tumor-free margins assessed microscopically after surgical resection. Our study is limited by its small sample size, retrospective nature, and unidentifiable confounding factors that could potentially affect outcomes. Larger scale studies are needed to investigate the effect of obesity on treatment outcomes in resectable and potentially resectable pancreatic cancer patients treated with neoadjuvant chemotherapy.[Table: see text]

e16246 Background: Obesity has been identified as a risk factor for pancreatic cancer. The prevalence of obesity has been on a rise in the last two decades. Obesity is defined by the world health organization (WHO) as body mass index (BMI) > 30.0 kg/m2. Studies have shown obese patients to have worse survival than non-obese patients with pancreatic cancer. However, there is limited data on effect of obesity on disease progression. We sought to identify the relationship between obesity and time to progression in patients with resectable and potentially resectable pancreatic ductal adenocarcinoma (PDAC). Methods: We performed a retrospective review of charts of all patients diagnosed with PDAC from 2017-2019 at Allegheny Health Network. Demographics (including age, sex, and race), treatment details, and time to progression date of diagnosis (rounded off in months) were obtained. Two-sided Mann-Whitney U test and Fischer’s exact test were used to evaluate differences between groups with continuous and categorical variables respectively. Furthermore, paired t test was used to compare mean time to progression between the patients in the obese and non-obese groups. A p-value of < 0.05 was considered as level of significance. Results: Out of the 121 patients who received treatment at our institution, 40 patients who had resectable or potentially resectable disease and had progression of disease were included in the analysis. The median age of patients was 68. The majority were females (60%), Caucasians (90%), had Stage I (65%) and potentially resectable disease (55%). Around 70% of patients were treated surgically, 80% received chemotherapy and 26% received radiation therapy. Twelve out of 42 patients were obese (27.5%). No difference in patient characteristics including demographics, staging, and treatment characteristics (proportion of patients who received surgery, chemotherapy, and radiotherapy) was identified between obese and non-obese group patients. The mean time to progression was 11.9 months in obese group as compared to 13.7 months in non-obese group (p = 0.63). Conclusions: Our study showed no significant difference in time to progression of disease between obese and non-obese patients with resectable/potentially resectable pancreatic cancer. Our study is limited by its small sample size, retrospective nature, and unidentifiable confounding factors that could potentially affect outcomes. Larger scale studies are needed to investigate the effect of obesity as a prognostic factor for disease progression in patients with pancreatic cancer.

BACKGROUND/AIM Cutaneous manifestations of disease are exceedingly rare and commonly overlooked in clinical practice. Allergies or contact dermatitis, autoimmune disease or skin cancer are the most common conditions typically associated with skin lesions. Rarely, cutaneous lesions may be the first sign of internal malignancy, or even resemble recurrent disease in those with history of cancer. CASE REPORT Herein, we report a case of an otherwise healthy male who presented to his primary care provider (PCP) with a skin lesion misdiagnosed as a furuncle, which eventually led to diagnosis of metastatic esophageal cancer. The patient was a 64-year-old male, presenting with a fungating lesion on the tip of his nose which was biopsied, confirming adenocarcinoma likely from a gastrointestinal source. Staging imaging showed extensive lung, liver, and boney metastatic disease. He was initially treated with chemotherapy and trastuzumab. CONCLUSION Cutaneous lesions are a rare presenting sign of malignancy, but rapidly growing lesions should be evaluated for possible metastatic disease.

A 23-year-old Caucasian woman, presented with recurrent fevers, elevated liver function tests and pancytopenia. Her labs at presentation were white blood cells 1.5 ×109/L, haemoglobin 8 g/L, platelets 59 k/mcl, lactate dehydrogenase (LDH) over 2000 U/L, aspartate aminotransferase 593 U/L, alanine aminotransferase 1321 U/L, alkaline phosphatase 223 U/L and ferritin 7665 µg/L. Epstein-Barr virus (EBV) IgM and IgG antibodies were positive in serum. A soluble interleukin 2 receptor was elevated at 2458. A bone marrow biopsy revealed scattered macrophages containing erythrocytes and other cellular elements. Immunohistochemistry for CD68 highlighted macrophages with erythrophagocytosis and in situ hybridisation was positive for EBV. She met the diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH). She was initially treated with broad spectrum antibiotics which were eventually discontinued once the diagnosis was established. Over a period of 2–3 weeks her fever, transaminitis, ferritin and LDH improved spontaneously. She continued to improve clinically and was subsequently discharged. HLH is an aggressive, life-threatening hyper-inflammatory syndrome which, if not promptly recognised and treated, can be fatal. Treatment involves etoposide-based chemotherapy and possible stem-cell transplantation. This patient showed signs of improvement spontaneously and a decision was made to not treat her. This was a rare case of EBV-associated HLH which resolved spontaneously without any intervention. This young patient was not subjected to unnecessary chemotherapy. So far only few cases of spontaneous resolution of EBV-associated HLH have been reported.

A leukemoid reaction is typically defined as white blood cell (WBC) count >50×109/L, predominantly neutrophil precursors, that are not due to tumour involvement in the bone marrow and not derived from clones. Leukemoid reactions associated with malignancy, known as paraneoplastic leukemoid reactions, are less common and are most notably seen with non-small cell lung cancer. A 64-year-old woman presented with right leg painful ulceration. On examination, she had multiple venous stasis ulcers more severe on the right, with no palpable pulses in her lower extremities. Her WBC count was 124×109/L and platelets were 517×109/L. Arterial dopplers showed limb-threatening arterial insufficiency which prompted right femoral endarterectomy. Few months earlier she was diagnosed with metastatic lung adenocarcinoma to the bone and she had leukemoid reaction with WBC 43.920× 109/L with 90% neutrophils. Repeat imaging showed progression of her malignancy and she passed shortly after. Inflammation is a key element of carcinogenesis and cancer progression. Among the different tumours, lung cancer is a non-haematologic malignancy that is most closely associated with leucocytosis. Some studies have found that leucocytosis was significantly associated with metastasis and shorter survival irrespective of other factors such as age or sex. The mechanism remains unclear however elevated levels of granulocyte colony-stimulating factor (CSF), granulocyte macrophage-CSF and interleukin 6 have been linked to this phenomena. The degree of leucocytosis seen in our patient is suggestive of CSF production leading to a paraneoplastic leukemoid reaction.

Background: There is a lack of empirical evidence that lockdowns decrease daily cases of COVID-19 and related mortality compared to herd immunity. England implemented a delayed lockdown on March 23, 2020, but Sweden did not. We aim to examine the effect of lockdown on daily COVID-19 cases and related deaths during the first 100 days post-lockdown.Methods: We compared daily cases of COVID-19 infection and related mortality in England and Sweden before and after lockdown intervention using a comparative-interrupted time series analysis. The period included was from COVID-19 pandemic onset till June 30, 2020.Results: The adjusted-rate of daily COVID-19 infections was eight cases/10,000,000 person higher in England than Sweden before lockdown order (95% CI: 2-14, P=0.01). On the day of intervention (lagged lockdown), England had 693 more COVID-19 cases/10,000,000 person compared to Sweden (95% CI: 467-920, PConclusion: The lockdown order implemented in England on March 23, 2020, effectively decreased the daily new cases rate and related mortality compared to Sweden. There was no short-term increase in COVID-19 cases and related-deaths after the phases one and two of the lifting of restrictions in England compared to Sweden. This study provides empirical, comparative evidence that lockdowns slow the spread of COVID-19 in communities compared to herd immunity.

Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that originates from plasmacytoid dendritic cells. It can involve skin, bone marrow, and/or lymph nodes. There is no consensus recommendation regarding treatment especially in the relapsed setting. Tagraxofusp, a CD123 directed agent, was recently approved by the Food and Drug Administration to treat BPDCN. We report a case of an elderly patient with diagnosis of BPDCN who was treated initially with tagraxofusp followed by azacitidine and venetoclax combination on relapse. Case report A 79 year old male presented with violaceous skin lesions. He had no other symptoms. Biopsy of these lesions was consistent with a diagnosis of BPDCN. Further testing showed no extracutaneous involvement. Management and outcome: Tagraxofusp was started at full dose (12 mcg/kg). This dose was not tolerated well. Patient could only tolerate the lowest dose (5 mcg/kg). Toxicities included elevated liver function tests, hyperglycemia, capillary leak syndrome, and pancreatitis. Dose escalation on progression was not possible due to side effects. Treatment was switched to venetoclax and azacitidine. Combination treatment was tolerated very well and patient showed major cutaneous response after 5 cycles and continues to do well. Discussion Tagraxofusp is a novel therapy that needs more real-world experience. This case describes the clinical course of an elderly patient on tagraxofusp. We also review the literature of azacytidine/venetoclax combination as a potential yet tolerable treatment option for this rare disease entity. This is the fourth case in literature to be treated with this combination.

Introduction One of the emerging targeted strategies for treatment of multiple myeloma (MM) is the use of robust immune responses via T cell activation against tumor cells. B-Cell Maturation Antigen (BCMA), a cell surface protein, remains a potential target for therapeutic interventions. Recently, bispecific T cell engager therapy, targeting BCMA and CD3 antigens on plasma and T cells respectively, have shown promising results in preclinical and early clinical studies in the context of relapsed/refractory myeloma (RRMM). We conducted a systematic review of phase 1 trials to report the efficacy and safety of Bispecific T-Cell Engager antibodies for MM. Methodology: We systematically searched multiple databases, including PubMed, Embase, Cochrane, and Clinicaltrials.gov. We also searched major conferences for oral or poster presentations. MeSH terms and keywords for MM and bispecific antibodies were utilized. We included all original studies reported in English language published from 1990 until June 2021. The primary database search yielded 390 articles. After excluding review articles, duplicates, irrelevant articles, and non-human studies, six phase 1 clinical trials were included to evaluate the efficacy and safety outcomes. Results: A total of 253 patients were identified from the six phase 1 studies, among whom 247 were evaluable for response, while the safely analysis involved all the patients. A study conducted by Krishan et al. (n= 40) stated an overall response rate (ORR) of 65% among patients receiving subcutaneous (SQ) teclistamab with a median of five prior therapies, 30% and 58% of the responders had a complete response (CR) and very good partial response (VGPR), respectively. A similar ORR of 63% was reported in 28 patients with a median of 5.5 prior therapies receiving SQ talquetamab by Berdeja et al. Cohen et al reported an ORR of 51.7% in patients receiving IV BFCR4350A at doses ≥3.6/20mg (Partial response (PR):17.2% and CR: 10.3%). SQ elranatamab achieved an ORR of 75% in 17 patients who received doses ≥215 μg/kg. Madduri et al. evaluated REGN5458 monotherapy with dose escalation from 3 to 96 mg among 45 patients and reported an ORR of 60% at the highest dose levels. ORR of 31% was reported in 42 patients receiving IV BI836909/AMG 420 by Topp et al. The median time to response (TTP) was 1 month in the majority of the studies. (Table 1) The most common grade three or higher hematological toxicities were neutropenia and anemia, while among non-hematological toxicities, infections were the most common. The incidence of cytokine release syndrome and neurotoxicity varied from 24% to 74% and 2 % to 20%, respectively. (Table 3) Conclusion: The early clinical data of Bispecific T-Cell Engager therapy in heavily pretreated RRMM patients shows promising results regarding its efficacy and safety profile. It represents a whole new horizon of targeted approach towards RRMM. Phase II / III studies are being conducted to evaluate this potential treatment approach in patients with MM. Figure 1 Figure 1. Disclosures Anwer: GlaxoSmithKline: Research Funding; BMS / Celgene: Honoraria, Research Funding; Allogene Therapeutics: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding.

Background It is known that malignant hypertension (mHTN) and thrombotic microangiopathy (TMA) commonly coexist. Deciding which phenomenon preceded the other remains a clinical dilemma, specifically in African American patients. However, making that determination is of utmost importance because the management will be different, and that can have dramatic effects on prognosis and outcomes. Herein, we report a case of atypical hemolytic uremic syndrome (aHUS) presenting as mHTN. Case Presentation A 35-year-old African American male with known history of hypertension, presented with nausea, vomiting, and diarrhea for four days. He also reported fatigue and exertional shortness of breath. Upon presentation, his blood pressure was 260/160 mmHg, otherwise physical exam was unremarkable. Initial work up showed hemoglobin of 8.8 g/dL (baseline 13.5), platelet count of 21,000/mL (baseline 250,000), serum creatinine of 16.99 mg/dL (baseline 0.99), MCV (84 fl), increased reticulocyte production index (3.58), increased LDH (1709 U/L), undetectable haptoglobin, and numerous schistocytes on peripheral blood smear. He was admitted as a case of hypertensive emergency and TMA. IV labetalol and hemodialysis were started. Given his gastrointestinal symptoms; stool for Shigella and E.Coli O157:H7 were checked and they were negative. Given the severity of his hematologic derangements and difficult to control blood pressure, we decided to proceed with renal biopsy to rule out primary aHUS which showed thrombotic microangiopathy, global glomerulosclerosis, moderate interstitial fibrosis and tubular atrophy suggestive of aHUS or rheumatologic disorders like systemic sclerosis and arguing against malignant HTN as the sole player. ANA and anti-Scl-70 antibodies were negative. Final impression was aHUS by exclusion, and patient received meningococcal vaccines (Menactra and Bexsero) in preparation to start eculizumab. aHUS genetic panel was sent which came back equivocal as it showed mutations of unknown significance (homozygous missense mutation in the MASP2 gene and 2 heterozygous mutations in the C2 gene). He was started on eculizumab 900 mg weekly for 4 weeks then 1200 mg biweekly starting week 5. He was seen in the office 2 months after initial presentation and receiving 5 doses of Eculizumab. His kidney function showed improvement with > 2 liters of urine output daily, blood pressure was better controlled. A decision by nephrology was made to give him a break from dialysis and remains dialysis-free a year later. Discussion aHUS is a rare disorder with an estimated prevalence of seven per one million children in Europe. It causes uninhibited activation of complement factors that leads to renal endothelial damage and activation of coagulation cascade leading to TMA. The diagnosis of aHUS requires the fulfillment of the classical triad (microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure) with a positive gene mutation or antibodies to complement factors. However, absence of these mutations or antibodies, as in the presented case, do not exclude the diagnosis. The early diagnosis of aHUS is necessary for treatment with eculizumab, a monoclonal antibody against C5 to block the terminal complement cascade. Kidney biopsy can be helpful in equivocal cases especially if it shows only the typical changes of malignant hypertension which essentially rules out aHUS. Hypertension with concurrent TMA is treated with strict BP control which is often enough to resolve TMA features and restores renal function, at least partially. On the contrary, aHUS causing severe HTN needs more sophisticated testing and blockade of the terminal complement component to improve outcome; that's why the distinction of which one is the primary process is of utmost importance. Our case emphasizes the importance of having low threshold for testing for aHUS in patients with mHTN and TMA, especially in African American patients where malignant HTN is known to happen more commonly, and to notice the subtle hints that may help in this distinction, such as profound hemolysis or thrombocytopenia out of proportion to what one would expect from mHTN alone. Early recognition of aHUS may save a patient's kidney. Disclosures No relevant conflicts of interest to declare.

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and other hematologic malignancies. However, its use is associated with serious adverse effects including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can present with aphasia, mutism, somnolence, seizures, signs of increased intracranial pressure and rarely cerebral edema. Corticosteroids (CS) and IL-6 inhibitors are first line treatment for CRS and ICANS. Prolonged CS use has been associated with decreased over-all survival in CAR T-cell treated patients. Data on effective treatments for CART T-cell induced neurotoxicity is limited, especially in steroid-refractory ICANS. Blood-brain barrier (BBB) disruption and infiltration of myeloid and immune effector cells into the central nervous system are implicated in the pathogenesis of ICANS. This likely explains the role of intrathecal chemotherapy, which has been described in literature for treatment of steroid-refractory ICANS. Here, we report the outcomes of two patients with refractory DLBCL who developed severe ICANS after receiving axicabtagene ciloleucel (axi cel) and treated with intrathecal (IT) chemotherapy. Case Presentation Our first case is of a 66 year old male with diagnosis of R/R DLBCL, who was treated with R-CHOP, followed by R-GemOx, with no response then received axi cel. Patient developed grade 2 CRS and grade 1 ICANS (National Cancer Institute Common Terminology Criteria for Adverse Effects v4.03) on day +2 post infusion, treated with tocilizumab and dexamethasone with good response initially. While tapering dexamethasone on day +5, he developed grade 3 CRS and grade 3 ICANS. Brain MRI did not show any intracranial abnormality and EEG showed no seizure activity. Lumbar puncture (LP) was done on day +7 and showed opening pressure of 32 cm H2O, and 12 lymphocytes. He was started on IV solumedrol and tocilizumab was resumed. CRS improved while neurotoxicity progressed to grade 4 prompting intubation and mechanical ventilation on day +8. On day +9, patient received intrathecal methotrexate 12 mg and hydrocortisone 50 mg. On day +12, neurotoxicity improved to grade 1 and patient was extubated on day +13. Steroid taper stopped on +17. Despite disease response, patient remained hospitalized at day +45 for deconditioning and vocal cord paralysis related to a lengthy hospital stay and intubation. He was eventually discharged, however passed away on day +49 from complications of prolonged hospitalization. Our second case is of a 69 year old female with a diagnosis of R/R DLBCL with CNS involvement, treated with RCHOP x6 followed by salvage chemotherapy with refractory disease, She then received axi cel. Patient developed grade 1 CRS on day +4, treated with tocilizumab and dexamethasone, and patient responded well. On day +9, she developed grade 2 CRS and grade 3 ICANS. At that time, dexamethasone was switched to pulse dose solumedrol and tocilizumab was continued. CT head showed no acute intracranial abnormality and EEG did not show any epileptiform activity. LP showed opening pressure of 21, and 84 lymphocytes. On day +11, patient's CRS resolved, however ICANS developed to grade 4 and patient received 12 mg intrathecal methotrexate and hydrocortisone 50 mg for steroid-refractory ICANS. The very next day, patient showed significant neurological improvement. Steroid taper was initiated and patient's ICANS resolved on day +16. MRI brain showed decrease in size of nodular enhancement along periventricular white matter and left occipital area corresponding to treatment response. She was discharged on day +28 and continues to do well one year out of axi cel infusion Conclusion Our abstract adds to the sparse literature about the use IT chemotherapy in cases with severe ICANS. It also highlights its importance as an alternative potential therapy to high doses and prolonged courses of corticosteroids which is associated with increased morbidity and mortality. Steroid-refractory ICANS has limited treatment options and further evaluation of the use of IT chemotherapy in large scale studies is warranted. Disclosures Kahn: Abbvie: Research Funding, Speakers Bureau; Astrazeneca: Research Funding, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Epizyme: Research Funding, Speakers Bureau; Genetech: Research Funding, Speakers Bureau; GSK: Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau; Morphosys: Speakers Bureau; Sanofi: Speakers Bureau; SeaGen: Speakers Bureau. Fazal: Agios: Consultancy, Honoraria, Speakers Bureau; AMGEN: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau; Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Lister: Oncology Analytics: Other: Academic Board.

Background and Objective: Disease relapse remains the primary cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Oral azacitidine (5-aza) was associated with clinical benefit as maintenance therapy in transplant ineligible patients. However, contradicting data have been reported regarding the role of 5-aza as a maintenance therapy to reduce relapse rate -post-allo-HSCT. We conducted this systematic review to describe the efficacy and safety of 5-aza in this context. Materials and Methods: We systematically searched multiple databases, including PubMed, Embase, Cochrane, and Clinicaltrials.gov. We also searched major conferences for oral or poster presentations. We used MeSH terms and keywords for MDS, AML, Allo-HSCT, and 5-aza. We included all retrospective and prospective studies of 5-aza (all formulations) published until March 2020. The primary database search yielded 1209 articles. We excluded irrelevant, duplicate, and review articles. The final search revealed 20 articles that we explored in detail for various efficacy and safety outcomes. Results: A total of 1211 patients were enrolled in 14 prospective and 6 retrospective studies. Of those, 1169 patients were evaluable. Prospective studies CALGB 100801 trial by Vij et al. (2015) reported overall survival (OS) of 45.7% and progression-free survival (PFS) of 41.2% at 24 months following reduced intensity conditioning (RIC) in a phase 2 trial of 41 patients. In a randomized control trial, Oran et al. (2018) evaluated relapse-free survival (RFS) as the primary outcome after 12 cycles of 5-aza at 32 mg/m2/day (n=187). Only 30% of the patients in the azacitidine arm completed the targeted number of cycles. The study showed a median RFS of 24.8 months in the treatment arm vs 15.3 months in the control arm (p=0.43). In a phase 2 trial conducted by Guillaume, T et al. (2019) the cumulative incidence of relapse was 27.6% in patients who received 5-aza, compared with 41.9% in 58 matched patients control group (p=0.21). Platzbecker et al. (2018-2019) studied a higher dose of azacitidine (75mg/m2/day) in a phase 2 trial as a pre-emptive strategy for patients who develop minimal residual disease (MRD) within 24 months. The 12-month OS and PFS were 94% and 44%, respectively. De Lima et al. (2018) studied the role of maintenance Oral 5-aza in Phase I/II trial (n=30). A dose-escalation design was used with a dosage ranging from 150 mg to 400 mg, received in a 7- or 14-day cycles. The 12-month PFS was 54% and 72% and estimated survival was 86% and 81% among 7-days and 14-days cycles, respectively. (Table 1) Retrospective studies: Mishra et al. (2017) reported a better OS in 14 patients who received 5-aza maintenance compared with a control arm (p-value 0.026). Cheikh et al. reported a 12-month OS of 70%. Ali, N et al. (2020) (n=107) compared 5-aza group vs. control group retrospectively. EFS was 53.1% vs. 49.5% (p=0.02) while OS was 56.8 and 53.4 months (p=0.01) in the treatment arm vs the control arm respectively. Safety: The most common grade 3 or 4 hematological adverse effect was neutropenia, while some patients also experienced grade 3 or 4 anemia, thrombocytopenia, or lymphopenia. The main non-hematological adverse effects were infections, fatigue, and gastrointestinal distress. The incidence of acute graft versus host disease varied from 13% to 50%. The most common reason for treatment discontinuation was disease relapse. A minority of patients discontinued treatment due to side effects. Conclusion: To our knowledge, this is the first comprehensive systematic review for the role of 5-aza maintenance -post-Allo-HSCT in patients with MDS or AML. The heterogeneity of the studies, in terms of dosing regimens, variable duration of treatment and patient selection, precludes definitive conclusions. Despite that, 5-aza seems to improve relapse rates and OS at least numerically but also significantly in some studies, as illustrated in this review. Low number of patients involved in most of these studies contributed to non-significant p-values. Azacitidine remains a valid and safe option, especially in patients with high risk of relapse. Further studies aiming at those high risk patients, such as AML with myelodysplasia related changes (AML-MRC) and high-risk MDS following RIC, are of utmost need. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Takeda: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Janssen: Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Speakers Bureau; Jazz: Consultancy, Speakers Bureau.