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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.

When two small fluid drops are sufficiently close, the van der Waals force overcomes surface tension and deforms the surfaces into contact, initiating coalescence. The dynamics of surface deformation across an inviscid gap falls into two distinct regimes (Stokes and inertial–viscous) characterized by the forces that balance the van der Waals attraction at leading order (viscosity, and both inertia and viscosity). The previously studied Stokes regime holds for very viscous drops but fails for less viscous drops as inertia becomes significant before contact is reached. We show that the subsequent inertial–viscous dynamics is self-similar as contact is approached, with the gap width decreasing as $t{'^{3/8}}$ and the radial scale of the deformed region decreasing as $t{'^{1/2}}$ as $t{'}\to 0$ , for time until contact $t'$ . The self-similar behaviour is universal and is the generic asymptotic behaviour observed in time-dependent simulations. The unique self-similar gap profile of the inertial–viscous regime suggests new initial conditions for the coalescence of the drops after contact.

PURPOSE Standard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy. PATIENTS AND METHODS One hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital. RESULTS Mean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed. CONCLUSION Subjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (

Background: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for hematopoietic stem cell transplant in the first-line setting and how it varied over time. Methods: We queried the National Cancer Database for patients diagnosed with MM between 2004 and 2016 and included only those who received systemic therapy as the first-line treatment. Enrollment rates for therapy were calculated as receipt of systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator) and used to calculate incident rate ratios that were further analyzed using Poisson regression analysis. A multivariate Cox proportional hazards model was constructed for survival analysis, and differences were reported as hazard ratios (HRs). Results: We identified 56,102 patients for enrollment analysis and 50,543 patients for survival analysis. Therapy enrollment in a multivariate model was significantly impacted by race and sex (p 1), whereas female sex, non-Hispanic black race, higher income, and treatment at an academic center were associated with improved survival (HR

When two small viscous drops are sufficiently close, van der Waals force overcomes surface tension and deforms the surfaces into contact, initiating coalescence. The dynamics of surface deformation across an inviscid gap are self-similar as contact is approached, with both radial and gap scales varying as t^{'1/3} for time until contact t^{'}. Van der Waals and viscous forces are dominant. The self-similar profiles are both nonuniversal and of the second kind: the observed t^{'1/3} behavior is selected only by the subdominant surface tension.

Purpose: Oral mucositis (OM) is a common, debilitating complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Supersaturated calcium phosphate rinse (SCPR) and palifermin have shown efficacy in preventing severe OM. However, whether their efficacy differs is unknown. We aimed to compare the efficacy of SCPR and palifermin in HSCT patients receiving myeloablative conditioning. Methods: A comprehensive review of our institutional database was performed to identify patients who received myeloablative-conditioning therapy over 5 years. Most patients received Fludarabine, Busulfan and total body irradiation (FBT). Results: We identified 26 patients who received SCPR and 122 patients who received palifermin for OM prophylaxis. The prevalence of World Health Organization (WHO) grade 3 or 4 OM was significantly lower in the palifermin group (57% vs 100%, p=0.01). In addition, the palifermin group had lower WHO grade 4 OM (22% vs 62%, p=0.0006). The overall prevalence of OM was not significantly different between the two groups (86% for palifermin group vs 100% for SCPR arm, p=0.15). Subgroup analyses demonstrated improved outcomes with palifermin, regardless of age, sex, disease status, donor type, and primary diagnosis. Conclusion: As compared to SCPR, the use of palifermin is associated reduced severity of OM in HSCT patients receiving radiotherapy-based myeloablative conditioning.

IntroductionPulmonary arterial hypertension (PAH) is a progressive, lethal, and incurable disease of the pulmonary vasculature. Evolving evidence indicates that the ubiquitin-specific proteases (USPs), play an important role in the pathogenesis of PAH by deubiquitinating key proteins involved in cell proliferation, migration, and apoptosis. Our genome-wide association study (GWAS) analysis-paired with transcriptomic profiling indicated that deubiquitinase USP11 and histidine triad nucleotide binding protein 3 (HINT3) are positively correlated and that their expression increased in lungs of PAH patients compared to control (fail donor) group, and inversely correlated with survival. However, mechanisms and function of the USP11/HNT3 axis have not been explored in PAH. Therefore, we aimed to investigate that HINT3 stabilized by USP11 activation links to endothelial apoptosis-resistance in PAH.Methods and ResultsExpression of USP11 and HINT3 was increased in the lungs of idiopathic PAH (IPAH) patients and Hypoxia/Sugen-treated mice using qRT-PCR and Western blot analyses. USP11 and HINT3 interacted physically as shown by co-immunoprecipitation (co-IP) assay in human pulmonary artery endothelial cells (HPAECs). HINT3 levels were decreased upon transfection of HA-tagged Ubi plasmid into HPAECs. Pretreatment with the potent proteasome inhibitor MG132 prolonged the half-life of HINT3 protein, indicating that HINT3 is degraded by polyubiquitination. HINT3 was stabilized and destabilized by forced overexpression or siRNA knockdown of USP11 respectively. Similarly, treatment with mitoxantrone, a USP11 antagonist, reduced HPAEC HINT3 expression. HINT3 interacted with the antiapoptotic mediator, BCL2. Overexpression of USP11 increased BCL2 content, congruent to elevated lung tissue levels seen in IPAH patients and Hypoxia/Sugen-treated mice. Conversely, knockdown of HINT3 function led to depletion of BCL2.ConclusionsThe HINT3-USP11 axis contributes to apoptosis-resistance in pulmonary artery endothelial cells, as is potentially a novel and attractive therapeutic target for ubiquitination modulators.

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.

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.

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

Introduction Although the safety and feasibility of rapid rituximab administration has been demonstrated for B-cell malignancies, there is scant data in the literature to support its use in patients with benign diseases. Objective To identify the incidence of infusion-related reaction with rapid rituximab administration in malignant and benign disease. Secondary objective was to determine the infusion time saved between standard administration and rapid rituximab administration. Methods A retrospective cohort study was conducted by reviewing electronic medical records from December 2018 to April 2020. Adult patients who received at least one dose of rapid rituximab were included. Results A total of 63 patents were included. The incidence of an infusion-related reaction with rapid rituximab was 1.6%. The one patient who reacted had a diagnosis of neuromyelitis optica. The mean infusion time saved was 2.9 hours (95% CI: 2.7-3.1; P-value Conclusion The use of the rapid rituximab administration is safe and well tolerated in both benign and malignant disease.

Mantle cell lymphoma is an aggressive and incurable subtype of non‐Hodgkin B cell lymphoma. Patients typically present with advanced disease, and most patients succumb within a decade of diagnosis. There is a clear and urgent need for novel therapeutic approaches that will affect mantle cell lymphoma through a unique mechanism compared to current therapies. This study examined the use of RNA interference (RNAi) therapy to attack mantle cell lymphoma at the mRNA level, silencing genes associated with cancer cell proliferation. We identified a lipid nanoparticle formulated with the lipidoid 306O13 that delivered siRNA to JeKo‐1 and MAVER‐1 mantle cell lymphoma cell lines. Three therapeutic gene targets were examined for their effect on lymphoma growth. These included Cyclin D1, which is a cell cycle regulator, as well as Bcl‐2 and Mcl‐1, which prevent apoptosis. Gene knockdown with siRNA doses as low at 10 nM increased lymphoma cell apoptosis without carrier‐mediated toxicity. Silencing of Cyclin D1 induced apoptosis despite a twofold “compensation” upregulation of Cyclin D2. Upon simultaneous silencing of all three genes, nearly 75% of JeKo‐1 cells were apoptosing 3 days post‐transfection. Furthermore, cells proliferated at only 15% of their pretreatment rate. These data suggest that lipid nanoparticles‐formulated, multiplexed siRNA “cocktails” may serve as a beneficial addition to the treatment regimens for mantle cell lymphoma and other aggressive cancers.

Background Bruton tyrosine kinase (BTK) inhibitors (ie, ibrutinib, acalabrutinib) are approved for treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and can mediate durable responses in some patients; however, relapses are common, primarily due to acquired mutations in BTK enzyme and/or phospholipase C gamma 2 (Albitar F, et al. J Cancer. 2015;6[5]:409-411. Maddocks KJ, et al. JAMA Oncol. 2015;1[1]:80-87. Woyach JA. Clin Adv Hematol Oncol. 2016;14[5]:330-333. Woyach JA, et al. N Engl J Med. 2014;370[24]:2286-2294.). Preclinical studies demonstrated successful generation and robust cytotoxicity of an autologous, non-genetically modified, polyclonal T-cell product (IOV-2001) from BTK-inhibitor-treated patients with CLL (Karyampudi L, et al. HemaSphere. 2019; 3[suppl 1; abstract PF447]), consisting of billions of peripheral blood lymphocytes (PBLs). Compared with pre-ibrutinib and treatment-naïve PBLs, those derived from post-ibrutinib blood samples demonstrated higher-fold expansion from peripheral blood and produced higher levels of IFNγ in response to non-specific T-cell receptor stimulation. Methods IOV-CLL-01 (NCT04155710) is an ongoing, first-in-patient, Phase 1/2, open-label, multi-cohort, dose-finding study designed to evaluate the safety and efficacy of IOV-2001 in patients with CLL/SLL who are progressing or have progressed on ibrutinib or acalabrutinib treatment. PBLs are generated by T-cell expansion from 50 mL of the patient's blood in a 9-day manufacturing process at a centralized GMP facility. The PBL product is then cryopreserved and sent back to the treatment center for infusion into the patient. Treatment consists of a preparative regimen of lymphodepleting chemotherapy (cyclophosphamide IV 500 mg/m 2 and fludarabine IV 30 mg/m 2) for 3 days, followed by 2 days of rest, a single infusion of IOV-2001, and 6 doses of either low-dose (9 MIU SC) or high-dose (600,000 IU/kg IV) interleukin-2 (IL-2; Figure 1). Approximately 1 to 5 clinical sites in North America will treat ~39 to 70 patients across 4 cohorts in 2 phases (Table 1). The primary endpoint for Phase 1 (Cohorts 1a and 1b) is to determine the recommended Phase 2 dose (RP2D) of IOV-2001 followed by IL-2, and for Phase 2 (Cohorts 2 and 3) is to evaluate efficacy of the RP2D of IOV-2001 followed by IL-2, as measured by objective response rate per investigator assessment. Patients ages ≥18 years, diagnosed with CLL/SLL with radiographically measurable disease, Eastern Cooperative Oncology Group performance status of 0-1, and meeting prior therapy criteria according to Table 2 are eligible for inclusion. Four US sites are currently active and enrolling patients. Figure 1 Figure 1. Disclosures Pinilla Ibarz: Sellas: Other: ), patents/royalties/other intellectual property; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau; AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory; MEI, Sunesis: Research Funding. Lister: Oncology Analytics: Other: Academic Board. Woyach: Gilead Sciences Inc: Other: Data & Safety; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee; AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding. Graf Finckenstein: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Jagasia: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Samakoglu: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Yadav: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Li: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Byrd: Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.

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.

Introduction Primary CNS lymphoma (PCNSL) is an aggressive form of lymphoid malignancy that occurs exclusively in the brain, meninges, spinal cord, and eyes. The incidence of PCNSL has been increasing, particularly in the elderly population, with a median age at diagnosis of 66 years (Olson J.E. et al., Cancer 2002). The primary modality of treatment for this deadly disease is systemic chemotherapy that includes high-dose methotrexate (HD-MTX), with or without whole-brain radiation. Due to the toxicity of HD-MTX, physicians tend to avoid using it in the elderly population. This was confirmed in previous reports from the 1990s (Panageas K.S. et al., Cancer 2007). In this comprehensive population-based analysis, we sought to examine the patterns of treatment and survival in elderly patients in the 2000s and sought to investigate clinical and socioeconomic predictors of treatment selection. Methods We conducted a retrospective cohort analysis using de-identified data accessed from the national cancer database (NCDB). The NCDB provided records of 2985 patients diagnosed with PCNSL between 2004 and 2015. We excluded patients who are younger than 65 years old, those who tested positive for HIV, and those who started treatment >120 days since diagnosis to account for immortal time bias. Patients were divided into four groups based on treatment received: combined modality treatment (CMT), chemotherapy alone, radiation alone, and no treatment. Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Multivariate regression models were used to analyze predictors of the selection of any treatment versus no treatment and for selecting chemotherapy versus no chemotherapy. To account for variable baseline characteristics, we used propensity score weighting methodology to calculate estimates of interest. Survival estimates were performed using the Kaplan-Meier method, and survival differences were tested using the wilcoxon-rank test. Results We identified 1096 patients with PCNSL who fulfilled the inclusion criteria. The median age was 73 (IQR: 68-79). There were 52% males. The majority of the patients were whites (92%), lived in a metropolitan area (78%), treated at an academic/research center (57%). The most common treatment modality used was chemotherapy alone (48%), followed by CMT (22%), no treatment (16%), and radiation alone (13%). On multivariate analysis, age (OR: 0.94, 95% CI 0.92-0.96) and comorbidity score (OR: 0.63, 95% CI 0.52-0.76) significantly predicted receiving any type of treatment. Both age (OR: 0.91, 95% CI 0.89-0.94) and distance (OR: 1.006, 95% CI 1.001-1.01) were predictors of receiving chemotherapy. Median follow up was 12 months (IQR: 3-44). Median OS in months for the four groups was: 43.1 for CMT, 19.4 for chemotherapy alone, 17.2 for radiation alone, and 2.3 for no treatment. (wilcoxon-rank test p-value: 75 year old had lower median OS in general, but receiving CMT had a survival advantage as well. (Figures 1 and 2) Conclusions The majority of PCNSL patients in our analysis received treatment. Our results showed an increased trend of chemotherapy use in elderly patients compared with earlier reports, where radiation alone was the most common treatment modality. The median OS of patients was longer compared with the 1990s data (17 vs. 7 months). CMT was associated with better OS compared with no treatment and chemotherapy alone. Although this was numerically better compared with radiation alone, it was not statistically significant. Younger patients and patients with lower comorbidity scores were more likely to receive treatment. Younger patients and patients who live further from the treating facility were more likely to receive chemotherapy. Longer distance may have led to less radiation use due to the need for complex planning and frequent visits associated with radiation therapy. Our study is limited by its retrospective nature, which makes it at risk of selection bias. Using propensity score weighting methodology strengthens our results. Also, the NCDB lacks certain pertinent variables, such as details of chemotherapy regimens, and toxicity information especially for radiation in the CMT arm which will have practical implications. Disclosures Fazal: Glaxosmith Kline: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau. Kahn:Genetech: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Seattle Genetics: Honoraria; Abbvie: Honoraria; Celgene: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria.

Introduction The ability of the neoplastic cells to escape from immune surveillance has been considered as a hallmark of cancer. The upregulation of programmed death-1 (PD-1) and programmed death ligand-1/2 (PDL-1) axis is a major immune escape pathway in multiple malignancies including classical hodgkin lymphoma (cHL). Disruption of PD1-PDL1/2 pathway using checkpoint inhibitors (CPIs) leads to reactivation of immune cells to attack malignant cells. CPIs have been studied in cHL in different settings. Here in, we did a systematic review and meta-analysis of phase II and III clinical trials that looked at the efficacy of CPIs in cHL Methods We did a comprehensive literature search, using 4 major databases (pubmed, embase, chocrane, and clinialtrials.gov). We used MeSH terms and related keywords that included all CPIs in generic and trade names, and cHL. We included phase II and III prospective clinical trials in patients > 18 year-old. We excluded case reports, case series, review articles, retrospective and observational studies, and phase I clinical trials. Initial search resulted in 1647 articles. After applying the inclusion and exclusion criteria, we had 13 articles that we explored in details. We stratified the articles according to CPIs and did a pooled-analysis of the complete response (CR) rate. Medcalc was used to do the statistical analysis. Results Of those 13 clinical trials, we had 12 phase II trials and 1 phase III trial. Nivolumab was studied in 7 trials (n=568), pembrolizumab in 5 trials (n=427), and camrelizumab in 1 trial (n=86). Table 1 shows the characteristics of these trials. (table 1) Four studies evaluated the efficacy of nivolumab in the relapsed/refractory (RR) setting. Armand et al (2018) evaluated the efficacy of nivolumab after autologous hematopoietic stem cell transplantation (auto-HSCT), the cohort in this study was divided into 3 groups: patients who received brentuximab vedotin (BV) after auto-HSCT, patients who are BV naïve, and patients who received BV before and/or after auto-HSCT. Overall response rate (ORR) and CR were 68% and 13%, 65% and 29%, 73% and 12%, respectively. Maruyama et al (2017) reported ORR and CR of 81.3% and 25%, in 16 Japanese patients received nivolumab in combination with BV. The ORR and CR in the remaining 2 trials were: 82% and 59%, and 85% and 67%. In the frontline setting, nivolumab showed ORR and CR of 84% and 67% (Ramchandren et al, 2019), 96%-100% and 53-85% (Brockelmann et al, 2019 in 2 different dosing regimens), and 100% and 72% (Yasenchack et al, 2019). Pooled analysis of all nivolumab trials showed CR rate of 47.4 % (95% CI 29.0-66.1) (figure 1) Pembrolizumab was evaluated in 4 clinical trials in the RR setting. Armand et el (2019) reported CR rate of 83% in 25 patients. Chen et al (2019) reported ORR and CR of 76.8 % and 26.1% in patients who relapsed after auto-HSCT and BV, 66.7% and 25.9% in patients ineligible for HSCT, and 73.3% and 31.7% in patients who relapsed after auto-HSCT with no prior exposure to BV. In combination with gemcitabine, vinorelbone , and doxorubicin, pembrolizumab showed ORR and CR of 100% and 93%, respectively. The only phase III clinical trial compared pembrolizumab vs BV in the RR setting showed ORR of 65.6% vs 54% and CR of 24.5% vs 24%, respectively. Only one study evaluated pembrolizumab in the frontline setting, ORR and CR of 100% in 30 patients received 3 cycles of pembolizumab followed by 4-6 cycles of doxorubicin, vinblastine, and dacarbazine. Pooled analysis of all pembrolizumab trials showed CR rate of 54.4% (95% CI 32.6-77.2) (figure 2) Only one trial evaluated the role of camrelizumab as monotherapy or in combination with decitabine. The combination regimen showed ORR and CR of 95% and 71% in CPIs naïve patients, and 52% and 28% in patients previously received CPIs. Camrelizumab monotherapy showed ORR and CR of 90% and 32% in CPIs naïve patients. Conclusion CPIs in cHL have showed high rates of response in the frontline and RR settings, with fairly acceptable toxicity profile. Their efficacy was studied post HSCT and BV, in BV naïve patients, and in HSCT-ineligible patients. Pembrolizumab and nivolumab were the 2 most studied CPIs. Future direction should focus on more studies in the frontline setting, the role of combined CPIs with other CPIs or with novel agents, to spare this relatively young population the long term toxicity of chemotherapy. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.Fazal:Jansen:Speakers Bureau;Jazz Pharma:Consultancy, Speakers Bureau;Stemline:Consultancy, Speakers Bureau;Glaxosmith Kline:Consultancy, Speakers Bureau;Gilead/Kite:Consultancy, Speakers Bureau;Amgen:Consultancy, Speakers Bureau;Novartis:Consultancy, Speakers Bureau;Agios:Consultancy, Speakers Bureau;BMS:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene:Speakers Bureau;Karyopham:Speakers Bureau;Incyte Corporation:Consultancy, Honoraria, Speakers Bureau;Takeda:Consultancy, Speakers Bureau.

Introduction Gray-zone lymphoma (GZL) is a rare lymphoid neoplasm initially described in 2005. The world health organization first recognized it as a separate entity in 2008. These tumors have intermediate morphologic and phenotypic features between diffuse large B-cell lymphoma and Hodgkin lymphoma. There is no treatment guidelines given the rarity of the disease, and being relatively a new entity. In this first population-based analysis of GZL, we focus on combined modality treatment (CMT; chemotherapy and radiation) versus chemotherapy alone as a primary treatment strategy. We sought to examine the effect of each modality on survival and investigate clinical and socioeconomic predictors of treatment selection and survival using the national cancer database (NCDB). Methods We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 2176 patients diagnosed with GZL between 2004 and 2016. We excluded patients without histologic or cytologic confirmation of the diagnosis or patient with unrecorded stage information. We also excluded patients who started treatment after 4 months of diagnosis to account for immortal time bias. Treatment was categorized as CMT or chemotherapy alone. Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Multivariate regression models were used to analyze the predictors of treatment selection and survival. We used propensity score matching methodology for the comparative survival analysis. Survival estimates were performed using the Kaplan-Meier method and survival differences were assessed using the log-rank test. Results We identified 1047 patients with GZL who were treated with CMT or chemotherapy alone between 2004 and 2016. The median age was 63 (IQR 47-74), there were 56.7% Males. The majority of the patients were non-Hispanic whites (80.7%), had insurance (96.1%), had comorbidity score of 0 (75.4%), belonged to a metropolitan areas (83.4%), and were treated at a comprehensive community cancer centers or academic programs (65.5% combined). Only 164 patients (15.7%) received CMT, while 883 (84.3%) received chemotherapy alone. Treatment selection was affected by clinical factors (age and advanced stage) but not socioeconomic factors. Median follow up for the 811 patients with available survival data was 28.8 months (IQR 12.36-50.25). The use of CMT and higher median income were associated with better survival, while increased age, higher comorbidity score, and presence of B symptoms were associated with worse survival. Median overall survival was significantly higher in CMT group compared with chemotherapy alone group (HR 0.541, 95% CI 0.351-0.833, p-value 0.005). Discussion Number of patients with GZL increased gradually over the years, which reflects increased insight and recognition of this disease entity. The use of CMT is continuously increasing over the years. Receiving CMT had a survival advantage over chemotherapy alone. In contrary to a multicenter retrospective analysis by Evans et al where advanced stage was the only important predictor of survival in GZL, our analysis showed other clinical and socioeconomic factors that affected outcomes. Radiation is associated with increased cost, it requires complex planning, and creates significant psychosocial burden, in addition to toxicity which could have contributed to its less use with older patients. A previous retrospective report showed no effect on survival with use of consolidative radiation in 37 patients. Larger sample size in our cohort could have contributed to a different outcome. Our study is limited by its retrospective nature and lack of certain pertinent variables, such as details of chemotherapy regimens. Being a relatively new entity limited median follow up to 2.4 years. Longer follow up and larger prospective studies are needed to evaluate the role of consolidative radiation in GZL and its toxicity. Our study adds to the sparse literature about GZL and identifies clinical and socioeconomic factors that can affect treatment selection and outcome that should be taken in consideration in future research. Figure 1 Disclosures Fazal: Jazz Pharma: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Kahn:AstraZeneca: Honoraria; Celgene: Honoraria; Seattle Genetics: Honoraria; Genetech: Honoraria; Abbvie: Honoraria; Beigene: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria.

Introduction Determining eligibility for autologous hematopoietic stem cell transplantation (Auto-HCT) is considered standard of care for patients with newly diagnosed multiple myeloma (MM). In addition to comorbidity score, age >65 years is still a commonly used criterion to deem patients ineligible for transplant. Here we report the outcomes of patients ³ 65 years with MM who underwent Auto-HCT following risk stratification using HCT-CI along with other eligibility criteria. Methods We performed a retrospective analysis of 102 patients, who underwent Auto-HCT between 1/1/1999 and 12/31/2018 at Allegheny Health Network Cancer Institute. Ninety two patients (90%) received conditioning with Melphalan 200 mg/m2. Median overall survival (OS) was estimated at day+100, day+180, 1, 2, 3 and 5 years post Auto-HCT. Non-relapse mortality (NRM) was assessed at day 100 post Auto-HCT. Results For a cohort of 102 patients, a total of 119 Auto-HCT were performed. Median age at transplantation for the entire cohort was 69.2 years (65.1 - 79.4 years). Thirty five (34.3%) patients were aged ³70 years. Median HCT-CI score was 3 (range: 0-8). Median time to Auto-HCT following diagnosis was 9.1 months (range: 4.7- 176.7 months). Median time to ANC500 and PLT20 was 13 days (range: 10-15) and 18.4 days (range:8-42) respectively. Median OS by Kaplan-Meier analysis for the entire cohort vs patients ³ 70 years at day+100, day+180, 1, 2, 3, and 5 years post Auto-HCT was 97.1%, 95.1%, 91.2%, 83.3%, 78.4%, and 63.7% respectively vs 100%, 100%, 97.1%, 82.9%, 77.1% and 68.6% respectively. Median OS in months for patients Conclusion Auto-HCT in patients with MM aged ³65 years is safe, effective and should be offered to all patients with a reasonably good performance status. A fully integrated approach is required to accomplish the needs of elderly patients including consideration for quality of life.

Hospitalized patients with hematological malignancy (HM) suffer an increased incidence of venous thromboembolism (VTE). We sought to identify risk factors and rate of VTE in hospitalized patients with HM using National Inpatient Sample (NIS) for the years 2011 to 2015. We used ICD-9 codes to identify patients with HM as the primary diagnosis and VTE as a secondary diagnosis for hospitalization. The rate of VTE was highest in patients with acute myeloid leukemia (6.6%) followed by acute lymphocytic leukemia (6.1%) and non-Hodgkin's lymphoma (6.0%). The highest risk of VTE occurred among patients with HM receiving chemotherapy (OR 1.68; 95% CI 1.567-1.809) followed by infection such as pneumonia (OR 1.31; 95% CI 1.201-1.436) and sepsis (OR = 1.66; 95% CI = 1.524-1.621). Chemotherapy had the highest risk of developing VTE during hospitalization followed by sepsis and pneumonia. The identification of patients with HM most at risk for VTE could be used to design and test prophylactic strategy.

2062 Background: High dose methotrexate-based regimens remain the most effective treatment against PCNSL but optimal consolidative strategy has yet to be determined. There is lack of high scale clinical trials comparing WBRT versus ASCT as consolidation therapy. Only two phase II randomized clinical trials (PRECIS and IELSG 32) have addressed this question. In this comprehensive national cancer database (NCDB) analysis, we examine the effect of WBRT versus ASCT on survival in PCNSL, we also sought to investigate clinical and socioeconomic predictors of treatment selection Methods: We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 16579 patients diagnosed with PCNSL between 2004 and 2016. We excluded patients who tested positive for HIV, and those who started chemotherapy > 120 days or started radiation > 365 days since diagnosis, to account for immortal time bias. Patients were divided into two treatment groups based on consolidation therapy: ASCT and WBRT. Multivariable regression models were used to analyze predictors of treatment selection. To account for variable baseline characteristics, we used propensity score weighting methodology. Survival estimates were calculated using the Kaplan-Meier and Cox proportional hazard regression methods Results: We identified 1620 patients with PCNSL who fulfilled the inclusion criteria. ASCT and WBRT were received by 197 patients and 1423 patients, respectively (Table). On multivariable analysis, increased age decreased the odds of receiving ASCT (OR 0.997, CI: 0.996-0.999, P

Background The treatment options in Multiple Myeloma (MM) are variable and may involve combinations of chemotherapy, immunomodulatory therapy, monoclonal antibodies and stem cell transplant. In the present study, we hypothesized that socioeconomic factors impact the treatment and survival of patients with MM who receive systemic therapy as firstline treatment. Methods We queried the National Cancer Database (NCDB) for patients with MM (ICD-0-3 code 9732) diagnosed from 2004-2016. We included only that received systemic therapy as first line treatment. Active MM patients were defined as those treated within 120 days of diagnosis. Enrollment rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy or TTI (denominator) and used to calculate incident-rate ratios that was further analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, 1, p-value Citation Format: Thejus Jayakrishnan, Veli Bakalov, Zena Chahine, John Lister, Rodney Wegner, Santhosh Sadashiv. Disparities in the enrollment to systemic therapy and survival for patients with multiple myeloma [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-212.

Background Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 22% of newly diagnosed non-Hodgkin's lymphoma per year in the United States. Combination chemoimmunotherapy with or without radiation therapy is recommended for the upfront treatment of DLBCL (Yang Liu, AJH,2019). A minority of patients undergo surgery prior to the initiation of systemic therapy for symptom relief or treatment of complications related to the disease. There are concerns on the delay in initiation of systemic therapy when surgery is performed and the potential impact on long term survival in this aggressive chemosensitive disease. We aimed to explore the characteristics of patients undergoing surgery prior to systemic therapy (sxfirst), the predictors for sxfirst and the survival outcomes. Methods We queried the National Cancer Database for patients with DLBCL (ICD-0-3 code 9680) diagnosed from 2006-2015. Inclusion criteria were patients that received systemic therapy as first-line course of treatment and excluded patients with incomplete or missing data for disease stage, treatment characteristics and follow-up. We also excluded patients who underwent biopsy procedures for diagnosis and local procedures such as tumor destruction or ablation. Subgroup analysis of patients that received sxfirst was performed. Time-to-initial therapy (TTI) was defined as time in days (d) from diagnosis to systemic therapy. Survival was measured in terms of months (m) from the day of diagnosis. Stepwise multivariate logistic regression analysis for predictors of sxfirst and propensity score adjusted survival analysis was performed. Results Of 208,748 patients with DLBCL, 138,096 patients met the inclusion criteria of whom 6,381 (4.6%) were sxfirst. The characteristics of sxfirst are summarized in Table 1. Median age was 66 (interquartile range IQR 55-75) years and 61.1% were males. Majority were non-Hispanic whites, had private or medicare insurance, had comorbidity score of 0 and stage I disease. Most patients were treated in comprehensive community cancer centers. The top 5 extra-nodal disease sites were gastrointestinal (26.2%), male reproductive system (16.4%), brain and spinal cord (6.4%), endocrine system (4.1%) and head and neck (3.0%). The median follow up was 47.6 (IQR 14.0-78.9) months. The predictors for sxfirst are described in Table 2. The following disease sites were associated with higher likelihood of sxfirst: male reproductive system (p-value=3 (p-value 0.007), more recent year of diagnosis, advanced stages of disease and presence of B-symptoms. The TTI for systemic therapy was delayed in sxfirst group - 34 (IQR 22-51) days vs. 21 (IQR 11-35) days, p-value Conclusion The findings of the present study are twofold. First, the present study describes the characteristics and predictors of sxfirst among DLBCL patients. Second, if surgery is absolutely necessary prior to systemically treating DLBCL, the study suggests that the delay does not seem to impact long term survival of these patients and is similar to the 5-year overall survival (64%) reported for DLBCL when all stages and treatment strategies are combined (seer.cancer.gov/statfacts/dlbcl). While there are unmeasured confounding factors as a result of the absence of adequate prognostic markers and treatment characteristics in the database, it is possible that surgery truly doesn't impact the survival outcomes significantly. Further evaluation of this practical question is warranted in large scale prospective studies. Disclosures Khan: Abbvie: Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Beigene: Honoraria; Seattle Genetics: Honoraria. Fazal:Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.