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INTRODUCTION: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. METHODS: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high-dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non-intensive (n = 131). RESULTS: There was no difference in progression-free (PFS; P = .224) or overall survival (OS; P = .167) in deferred patients who received non-intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. CONCLUSIONS: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.

Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD>24, defined as POD >24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD>24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD>24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.

Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000-2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age < 65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2-year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2-year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA (p < 0.001). Two-year PFS rates were 79%, and 67% and 2-year OS rates were 92% and 86% for ages < 65 and ≥ 65 respectively (p < 0.001). First-line high-dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high-dose cytarabine-based induction can mitigate the negative impact of age on survival.

Background: Primary effusion lymphoma (PEL) is a rare, B cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, that is strongly associated with HIV infection. PEL often presents as malignant body cavity effusions but can also present as extracavitary masses. Patients may also have concurrent Kaposi sarcoma (KS) or multicentric Castleman disease (MCD). 80% of PEL is also positive for EBV, and in a cohort of 20 patients we previously showed EBV + PEL had improved overall survival (OS) (Lurain et al. Blood 2019). PEL prognosis is poor compared to other HIV-associated NHL with median survival of 6-10 months. While patients are often treated with chemotherapy regimens used in other NHL, the optimal front-line and subsequent-line treatments are unknown. In this largest cohort of patients with PEL in the United States, we evaluated survival, prognostic markers, and second-line treatments in relapsed/refractory disease. Methods: We analyzed clinical records of all patients with PEL treated in the HIV and AIDS Malignancy Branch at the National Cancer Institute from 2000-2021. We collected demographics, disease characteristics, concurrent KS and MCD, EBV status of tumor by EBER staining, and laboratory data at diagnosis as well as at progression and subsequent lines of therapy. We calculated overall survival (OS) of all patients and progression-free survival (PFS) in those who received front-line EPOCH by Kaplan-Meier method. The survival of extracavitary vs. cavitary PEL was compared using an exact log-rank test. A univariate Cox proportional hazard model was performed to determine prognostic variables associated with OS. Results: We identified 40 patients with PEL: 38 cisgender men, 2 cisgender women; 18 non-Hispanic Black, 6 Hispanic, 16 non-Hispanic White; median age 41 years. At diagnosis of PEL, 29 patients had concurrent KS, and 7 had concurrent MCD. Eight patients had only extracavitary disease, and 5 had leptomeningeal disease. All but 1 had HIV, and all with HIV received antiretroviral therapy. At diagnosis, median HIV viral load (VL) was 50 (IQR: 27-8323) copies/mL, median CD4 + cell count was 100 (IQR:44-395) cells/µL, and median KSHV VL was 4147 copies/10 6 cells (IQR:178-68,526). One patient died prior to receiving treatment. Of the 39 patients who received front-line treatment, 38 received combination chemotherapy (EPOCH [36], CHOP [1], ICE [1]) with rituximab added in 34 patients to treat concurrent MCD or deplete the KSHV-infected B cell reservoir. One patient received pembrolizumab as up-front therapy due to concurrent progressive multifocal leukoencephalopathy. Twenty-three (57%) had complete remission (CR) by Lugano criteria. Median PFS after front-line EPOCH was 16.4 months (Figure 1a), and median OS in all patients was 35.6 months (Figure 1b), with 5-year OS of 44%. Median OS for patients with extracavitary disease was significantly higher than in patients with cavitary disease (p=0.023, Figure 1c). EBER-positive tumors (HR=0.21, p=0.005) were associated with improved survival, while concurrent KS, MCD, leptomeningeal disease, and baseline CD4 and KSHV VL were not associated with OS outcomes. Eleven patients with relapsed/refractory disease received second-line therapy, including combination chemotherapy (3); brentuximab (3); pembrolizumab (1); pembrolizumab and pomalidomide (1); interferon-alpha, ganciclovir, and bevacizumab (1); bortezomib, ganciclovir, and zidovudine (1); and radiation to pelvic lymph nodes (1). Five of these patients received subsequent treatment after disease progression, including 2 patients with leptomeningeal PEL, 1 who received daratumumab and 1 who received pomalidomide and pembrolizumab with ongoing CRs at 12 months and 33 months, respectively. Conclusion: Patients with PEL had a median OS of 35.6 months, which is improved from previous reports. Patients with extracavitary PEL appear to have improved OS, and we confirmed our prior study noting EBER-positive PEL is a positive prognostic marker. Promising chemotherapy-sparing treatment regimens in relapsed/refractory PEL, include pembrolizumab, pomalidomide, and daratumumab. Figure 1 Figure 1. Disclosures Uldrick: Regeneron: Current Employment; Roche: Research Funding; Merck: Other: Receives study drug; Celgene: Research Funding. Yarchoan: Celgene: Research Funding; Merck: Other: Clinical Trial Support; EMD-Serano: Other: Clinical Trial Support; Eli Lilly: Other: Clinical Trial Support; CTI BioPharma: Other: Clinical Trial Support; Janssen Pharmaceuticals: Other: Clinical Trial Support; U.S. Dept of Health and Human Services: Patents & Royalties. Lurain: EMD-Serrono: Research Funding; BMS-Celgene: Research Funding; CTI Biopharma: Research Funding; Merck: Research Funding; Janssen: Research Funding.

Background Autologous stem cell transplant (ASCT) is frequently used as a consolidative therapy option after induction treatment in fit patients with mantle cell lymphoma (MCL) with the goal of prolonging the initial response duration. Despite recent advances there remains a subset of patients who experience early disease relapse after ASCT. We examined predictors of shortened progression-free survival (PFS) and post-relapse overall survival (OS) in a cohort of patients completing ASCT in first remission. Methods We evaluated MCL patients treated at 10 US academic medical centers. Eligible patients were treated from 2000 through 2017, and we collected information on demographic, clinical, and treatment-related variables of interest. Patients were then categorized into three post-ASCT PFS groups: 0-2 years, 2-5 years, and > 5 years, with PFS determined from the date of ASCT until progression or death from any cause. Patients followed for at least 5 years post-ASCT who were relapse free were included in the > 5 sub group. Associations were examined between groups and collected characteristics using chi-squared tests for categorical patient characteristics and ANOVA for numeric patient characteristics. The Kaplan-Meier method was used to estimate overall survival (OS) for each group, using time of relapse after ASCT as the starting point. Results Of 968 total MCL patients, 242 patients completed ASCT in first remission and either had a PFS event or were relapse-free for at least 5 years post-ASCT. Patients were 80% male, and the median age was 59 (Range: 29-83). The patients were divided into groups of post-ASCT PFS 0-2 years (n=74), 2-5 years (n=75), and more than 5 years (n=93). Post-ASCT PFS was shorter in patients with stage 4 disease (p=0.022), splenomegaly at baseline (p=0.005), and a lymph node size > 5 centimeters at baseline (p=0.043). Other variables were not significantly associated with PFS, including time to transplant and use of intensive therapy. Patients with 0-2 year PFS had a shorter median OS (22.1 months, 95% CI: 13.1- 38.1 months) in comparison to 2-5 year PFS (132 months, 95% CI: 36-132 months) and 5+ year PFS not reached (95% CI: 41.2 – N.A; Figure). Conclusion Patients with higher tumor burden at baseline have a shorter post-ASCT PFS and are more likely to relapse within 2 years. As has been seen in other lymphoma subtypes, early relapse is associated with shorter OS. This represents a patient group requiring improved therapies and perhaps are the best candidates for post-ASCT maintenance or consolidation approaches. Further studies integrating minimal residual disease and molecular risk-stratification may better identify patients at high risk for early progression.

Clinical classification of early dementia and mild cognitive impairment (MCI) is imprecise. We reported previously that molecular imaging classification of early dementia and MCI with dual amyloid and dopamine terminal positron emission tomography differs significantly from expert clinical classification. We now report pathological diagnoses in a substantial subset of our previously imaged subjects. Among 36 subjects coming to autopsy, imaging classifications and pathological diagnosis were concordant in 33 cases (κ = 0.85). This approach enhanced specificity of Alzheimer's disease diagnosis. The strong concordance of imaging-based classifications and pathological diagnoses suggests that this imaging approach will be useful in establishing more accurate and convenient classification biomarkers for dementia research. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696

Innovative strategies are needed to reduce the hypertension epidemic among African Americans. Reach Out was a faith-collaborative, mobile health, randomized, pilot intervention trial of four mobile health components to reduce high blood pressure (BP) compared to usual care. It was designed and tested within a community-based participatory research framework among African Americans recruited and randomized from churches in Flint, Michigan. The purpose of this pilot study was to assess the feasibility of the Reach Out processes. Feasibility was assessed by willingness to consent (acceptance of randomization), proportion of weeks participants texted their BP readings (intervention use), number lost to follow-up (retention), and responses to postintervention surveys and focus groups (acceptance of intervention). Of the 425 church members who underwent BP screening, 94 enrolled in the study and 73 (78%) completed the 6-month outcome assessment. Median age was 58 years, and 79% were women. Participants responded with their BPs on an average of 13.7 (SD = 10.7) weeks out of 26 weeks that the BP prompts were sent. All participants reported satisfaction with the intervention. Reach Out, a faith-collaborative, mobile health intervention was feasible. Further study of the efficacy of the intervention and additional mobile health strategies should be considered.

INTRODUCTION The optimal frontline treatment for mantle cell lymphoma (MCL) is not clearly defined. Bendamustine + rituximab (BR) is commonly used as initial therapy. The role of maintenance rituximab (MR) after BR is not agreed upon due to limited data supporting this practice, whereas MR improves overall survival (OS) after autologous stem cell transplant (ASCT) and after R-CHOP for elderly patients who do not receive ASCT. Preliminary results from a subgroup analysis of the randomized phase 3 MAINTAIN study revealed neither a progression-free survival (PFS) nor OS benefit for MR as compared to observation for MCL pts (Rummel, ASCO 2016). In follicular lymphoma patients, however, there does appear to be a PFS benefit to rituximab maintenance following BR. Given these disparate results, we sought additional data to evaluate the role of rituximab maintenance following BR in MCL METHODS MCL pts treated at 12 U.S. medical centers with frontline BR who achieved a complete response (CR) or partial response (PR) and who did not receive consolidative ASCT from 2011 - 2017 were included. Use of MR was based on individual physician/patient preferences. Baseline pt characteristics were compared using chi-squared test, Fisher's exact tests, or ANOVA. Descriptive statistics, comparisons, and OS using the Kaplan-Meier method were stratified by response status as determined by the treating site (complete response (CR) only, partial response (PR) only, and CR/PR). RESULTS Among 135 pts responding to frontline BR who did not complete subsequent ASCT, 80% achieved complete remission (CR) and 20% had a partial remission (PR). Median age was 70 (range 45 - 93) years and 66% were male. Baseline MIPI score was low (13%), intermediate (38%), or high (49%) among patients with available data (n = 92) and did not differ between treatment cohorts. Among responding patients, 78 (58%) received MR and 57 (40%) were observed. With a median follow up of 3.1 years, median OS was not reached for pts responding to BR (with CR or PR) who received MR vs. 6 years for those who received no maintenance (Figure Panel A, P = 0.0013). Use of MR vs. observation was associated with a significant improvement in OS for pts in PR at the end of induction therapy (Figure Panel B, median not reached vs. 1.7 years, P = 0.006), but there was no statistically significant OS difference for pts in CR (Figure Panel C, median not reached vs. 9.6 years, P = 0.2575). In multivariable analysis, MIPI score CONCLUSIONS Whereas the MAINTAIN trial showed no PFS advantage to MR after BR for MCL pts, in this multi-center outcomes analysis across multiple US centers, the use of MR was associated with an improvement in OS in pts receiving frontline BR without consolidative ASCT. The survival benefit was only observed for pts in PR after induction therapy. Because of the potential for selection bias in the application of MR, further validation cohorts and prospective study are needed to clarify if there is benefit to maintenance therapy after BR-treated patients not undergoing ASCT as well as the potential for differential benefit of maintenance based on remission status Disclosures Hill: Takeda: Research Funding; Amgen: Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Martin:Janssen: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Sandoz: Consultancy; Karyopharm: Consultancy; Teneobio: Consultancy. Calzada:Seattle Genetics: Research Funding. Kolla:Amgen: Equity Ownership. Bachanova:Gamida Cell: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; GT Biopharma: Research Funding; Novartis: Research Funding. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Celgene: Research Funding; Merck: Research Funding; Mundipharma: Honoraria; Seattle Genetics: Honoraria, Research Funding; Celgene: Research Funding; Mundipharma: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Research Funding. Danilov:Curis: Consultancy; Bristol-Meyers Squibb: Research Funding; TG Therapeutics: Consultancy; Abbvie: Consultancy; Genentech: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Takeda Oncology: Research Funding; MEI: Research Funding; Pharmacyclics: Consultancy; Aptose Biosciences: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Seattle Genetics: Consultancy; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Celgene: Consultancy; Janssen: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Ghosh:Celgene: Consultancy, Research Funding, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Speakers Bureau; Spectrum: Consultancy, Speakers Bureau; Astra Zeneca: Speakers Bureau; Forty Seven Inc: Research Funding; Genentech: Research Funding; Gilead/Kite: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Park:G1 Therapeutics: Consultancy; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Hamadani:Otsuka: Research Funding; Merck: Research Funding; Celgene: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Pharmacyclics: Consultancy; Medimmune: Consultancy, Research Funding; Takeda: Research Funding. Kahl:Seattle Genetics: Consultancy; BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Flowers:Optimum Rx: Consultancy; Acerta: Research Funding; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; National Cancer Institute: Research Funding; TG Therapeutics: Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Millenium/Takeda: Research Funding; V Foundation: Research Funding; Karyopharm: Consultancy; BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Denovo Biopharma: Consultancy. Cohen:Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Genentech, Inc.: Consultancy, Research Funding.

Introduction: Smoking is a potential risk factor for the development of non-Hodgkin lymphoma (NHL), and prior studies have reported inferior survival in tobacco users with certain subtypes of the disease (Taborelli et al, BMC Cancer, 2017; Ollberding et al, Br J Haematol, 2013). For instance, tobacco smokers with NHL had an inferior overall survival (OS) compared to non-smokers in a series of 471 patients who were managed up front with either chemotherapy (68%), radiation (27%), or observation, and this appeared to be most pronounced in patients with follicular lymphoma and in those with a 20+ pack year smoking history (Geyer et al, Cancer, 2010). The impact of tobacco use on survival specifically in patients with mantle cell lymphoma (MCL) has not been well studied. We conducted a multicenter study in MCL and evaluated the prognostic impact of tobacco use. Methods: We included patients with MCL from 12 sites who were ≥18 years old and for whom smoking status was known at the time of diagnosis. Cases were evaluated for reported smoking status at the time of diagnosis (active smoker, prior smoker, or never smoker) and standard baseline clinical prognostic data were obtained for each patient. Descriptive statistics were generated for these characteristics and were then compared across smoking status using chi-squared tests, Fisher's exact tests, or ANOVA, where appropriate. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method, and were compared using log-rank tests. Results: Of 946 included patients, 456 (48.2%) reported never using tobacco, 360 (38.7%) reported prior tobacco use, and 130 (13.7%) reported active tobacco use at the time of diagnosis. Median age was 59 in the active smoker group, 65 in prior smokers, and 61 in never smokers (p < 0.001). Any major medical comorbidity (defined as the presence of CAD, CHF, diabetes, CKD, ESRD, COPD, DVT, prior malignancy, or cirrhosis) was present in 59 (45.4%) of the active smokers, 143 (39.7%) of the prior smokers, and 140 (30.7%) of the never smokers (p = 0.002). Intensive induction regimens were used in 58.2% of active smokers, 47.2% of prior smokers, and 58.4% of never smokers (p=0.007). There were no significant differences between groups in regards to sex, race, ECOG performance status, Ann Arbor stage, time to first treatment, and use of auto transplant in first remission. Patients with no prior history of tobacco use were less likely to have a high risk MIPI score at diagnosis (26% high risk) compared to prior smokers (39.5%) and active smokers (32.5%, p=0.019). With a median follow up of 3.5 years after diagnosis, there was no significant difference between the 3 groups with regards to PFS or OS (Figure 1). Five-year OS in the never smoker group was 79.8% (95% CI: 74.8%, 83.9%) vs 75.1% (64.5%, 82.9%) in the active smoker group, and 80.6% (74.6%, 85.3%) in the prior smoker group (log rank p = 0.4079). Five- year progression free survival was 50.4% (44.6%, 56.0%) in the never smoker group, 42.5% (32.2%, 52.5%) in the active smoker group, and 50.2% (43.5%, 56.6%) in the prior smoker group (log rank p= 0.3595). Conclusions: Our data suggest that active or prior smoking does not significantly impact OS or PFS in patients with MCL. This study is limited by the fact that amount of current or former tobacco use was not available and it is not known how many current tobacco users ultimately stopped smoking during the course of their treatment. Future studies should incorporate more specific information regarding smoking history including pack-years and time between discontinuation of tobacco use and date of diagnosis. While tobacco use and other modifiable cardiovascular risk factors should be addressed as appropriate for all patients with MCL, current and former tobacco users can still achieve prolonged PFS and OS and may be candidates for intensive treatments after consideration of their other comorbidities and disease-specific risk factors. Disclosures Calzada: Seattle Genetics: Research Funding. Kolla:Amgen: Equity Ownership. Bachanova:Gamida Cell: Research Funding; GT Biopharma: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Celgene: Research Funding; Novartis: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Gerson:Seattle Genetics: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Takeda: Research Funding; Merck: Research Funding; Mundipharma: Honoraria; Bayer: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding. Danilov:Celgene: Consultancy; Abbvie: Consultancy; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Janssen: Consultancy; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Bristol-Meyers Squibb: Research Funding; MEI: Research Funding; Pharmacyclics: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Curis: Consultancy; Takeda Oncology: Research Funding; Seattle Genetics: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Hill:Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ghosh:Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Genentech: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Forty Seven Inc: Research Funding; Gilead/Kite: Consultancy, Speakers Bureau; Spectrum: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Astra Zeneca: Speakers Bureau. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Hamadani:Pharmacyclics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Otsuka: Research Funding; Takeda: Research Funding. Kahl:TG Therapeutics: Consultancy; BeiGene: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Martin:Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Teneobio: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy. Flowers:Karyopharm: Consultancy; Denovo Biopharma: Consultancy; Burroughs Wellcome Fund: Research Funding; AbbVie: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding. Cohen:Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding.

Background: Early progression of disease (POD) in patients (pts) with mantle cell lymphoma (MCL) following intensive frontline treatment has been associated with inferior survival (Dietrich et al Ann Oncol 2014 and Visco et al Br J Haematol 2019), but the optimal time point to define early POD and the predictive significance of early POD following less intensive frontline treatment is not well established. We compare outcomes after all frontline treatments in a large MCL cohort categorized by time to progression and describe outcomes by class of second line treatment for pts with primary refractory disease. Methods: Clinical and outcome data for MCL pts treated between 2000 and 2017 were collected from 12 US centers. Overall survival (OS), defined from time of 1st progression, and secondary progression free survival (PFS2), defined from 1st progression to 2nd progression or death, were estimated by Kaplan-Meier and compared by log-rank test. Univariable and multivariable analyses were performed using Cox proportional hazards models for OS. 95% confidence intervals were calculated for all estimates and displayed in square brackets. We defined intensive treatment as high dose cytarabine in frontline therapy and/or autologous stem cell transplant in 1st remission. Pts were categorized into three groups: (a) refractory disease to frontline therapy or POD within 6 months of frontline therapy was termed primary refractory (PRF); (b) POD between 6 to 24 months of therapy was termed POD24 and (c) POD beyond 24 months was termed POD>24. Salvage therapy was categorized as chemoimmunotherapy (CIT) for pts treated with CIT alone, BTK inhibitor (BTKi) for pts treated with BTKi single agent or in combination, and lenalidomide / bortezomib for pts treated with one or both agent +/- anti-CD20 therapy. Results: Of 1,168 pts with MCL, 457 pts had relapsed and were included in this analysis. The median age was 62, 77% were male, and ECOG PS was 0/1 in 94%. Median follow-up was 2.6 years (yr) after first progression. The most common induction regimens were R-HyperCVAD (26%), R-CHOP (24%), bendamustine and rituximab (19%), and R-M-CHOP (10%). Frontline treatment was intensive in 54%. Sixty five pts (14%) were PRF, 153 (34%) had POD24, and 239 (53%) had POD>24. Additional baseline characteristics and comparison between groups are summarized in Table 1. The median OS was 1.3 yr [0.9-2.4] for PRF pts, 3 yrs [2-6.8] for POD 24, and 8 yrs [6.2-not reached (NR)] for POD>24 (p24 pts (p Among pts with PRF MCL, median PFS2 and OS were 1.2 [0.5-2.3] and 2.4 [0.7-4.5] yrs for BTKi (n=21), 0.5 [0.2-2.3] and 1.1 [0.5-NR] yrs for CIT (n=22), and 0.3 [0.1-0.6] and 1.9 [0.1-2] yrs for lenalidomide / bortezomib (n=8) as 2nd line therapy. Two pts with PRF MCL received no further therapy and both died within one month of POD. Conclusions: Time to relapse is predictive of outcome in pts with MCL and outcomes with current salvage therapies are poor for pts with relapse within 6 months of frontline therapy. Of currently available second line therapies, BTKi were associated with improved PFS2 in refractory pts. Outcomes are particularly poor for pts who receive intensive induction therapies yet still relapse early, representing a population at high risk for early mortality related to MCL. Novel treatment approaches should be evaluated in this population, including CAR-T cell therapy, and attempts to improve risk stratification at diagnosis and develop improved therapies for high-risk pts should continue. Disclosures Maddocks: Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Merck: Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees. Kolla:Amgen: Equity Ownership. Bachanova:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Research Funding; Novartis: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Celgene: Research Funding; GT Biopharma: Research Funding. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Merck: Research Funding; Mundipharma: Honoraria; Bayer: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria. Hill:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Martin:Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Danilov:Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Bristol-Meyers Squibb: Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; TG Therapeutics: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Grover:Seattle Genetics: Consultancy. Karmali:Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Ghosh:AstraZeneca: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Research Funding; Forty Seven Inc: Research Funding. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Hamadani:Pharmacyclics: Consultancy; Merck: Research Funding; Celgene: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Otsuka: Research Funding; Medimmune: Consultancy, Research Funding; Takeda: Research Funding. Kahl:BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy. Flowers:Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; Denovo Biopharma: Consultancy; National Cancer Institute: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Bayer: Consultancy; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Karyopharm: Consultancy; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy. Cohen:LAM Therapeutics: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Astra Zeneca: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Hutchison: Research Funding; UNUM: Research Funding.

Introduction: Mantle cell lymphoma (MCL) is a rare form of lymphoma with no current standard of care. As a result, clinical trials are critical to improving our understanding of the disease and its management. However, clinical trial participation is often limited due to lack of access to studies, restrictive eligibility criteria, and decisions by treating physicians or patients not to participate. We evaluated the rate of enrollment and outcomes associated with clinical trial participation of patients with MCL at 12 US Medical Centers. Methods: We included patients from 12 medical centers in the United States with MCL diagnosed between January 1, 2000, and January 1, 2018, who were ≥ 18 years old, received any induction therapy, and for whom it was known whether initial treatment was on a clinical trial (CT) or not. We compared differences between the two groups (CT vs not) using Fisher's Exact and Chi-square tests as appropriate. We defined overall survival (OS) as time from diagnosis to death. Patients not experiencing an event were censored at their last known follow-up. OS was determined using the Kaplan-Meier method, and univariate and multivariable models were developed to identify predictors of OS. Results: Eight hundred twelve patients were included in this analysis, including 164 (20%) patients who participated in a clinical trial during initial therapy. Rate of participation ranged from 4% to 36% across contributing sites. Median age for the entire cohort was 62 years, 572 (74%) of patients were male, and 95% of patients had ECOG 0-1. MCL International Prognostic Index (MIPI) risk score was high in 163 patients (31%), and 84% of patients had stage IV disease. Ki67 was >30% in 169/225 (43%) patients with available data, and 19% of patients (65/271) had a complex karyotype with > 3 chromosomal abnormalities. Four hundred sixteen (53%) of patients received an intensive induction regimen (defined as initial treatment with a high-dose cytarabine-containing regimen and/or receipt of autologous hematopoietic cell transplantation as consolidation), including 333 patients (43%) who underwent transplant consolidation. Patients with an increased lactate dehydrogenase (LDH) level (p 3 cytogenetic abnormalities (p=0.015) were less likely to participate in clinical trials, but there was no significant difference in rates of participation based on MIPI (p=0.49) or ECOG performance status (p=0.22; Table). Patients treated on study were less likely to receive an intensive regimen compared to those treated off study (p=0.002). Median time to treatment from diagnosis was 35 days for patients enrolled on trial and 31 days for patients not enrolled on trial (p=0.83). With a median follow-up of 3.8 years, the median OS was 13.6 years (95% CI: 11.5-21.1) for patients not treated on a trial and not reached (95% CI: 9.9 - Not Reached) for patients treated on trial (Figure; p=0.036). In a multivariable model including clinical trial participation, MIPI, time to initial treatment, and receipt of an intensive induction regimen, only clinical trial participation (HR 0.54, 95%CI: 0.31-0.93; p=0.028) and high risk MIPI score (HR 4.24, 95% CI: 2.37-7.56; p Conclusions: Participation in a clinical trial is associated with improved OS among patients with untreated MCL, even when accounting for time to initial treatment and MIPI score. This study is unable to account for other factors that may predict trial participation including baseline comorbidities, socioeconomic status, social support, and distance to the treating center that are frequently factors that limit trial participation. However, these findings do suggest that enrollment on a clinical trial frequently leads to a successful outcome for patients in addition to providing answers to key clinical questions and should be considered for all eligible patients. Disclosures Cohen: Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; UNUM: Research Funding; LAM Therapeutics: Research Funding; Hutchison: Research Funding; Genentech, Inc.: Consultancy, Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Astra Zeneca: Research Funding. Calzada:Seattle Genetics: Research Funding. Kolla:Amgen: Equity Ownership. Bachanova:Incyte: Research Funding; Novartis: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Research Funding; GT Biopharma: Research Funding; Celgene: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding. Danilov:MEI: Research Funding; Seattle Genetics: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Curis: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Celgene: Consultancy; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; Bayer Oncology: Consultancy, Research Funding; Bristol-Meyers Squibb: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution. Hill:TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding. Ghosh:Spectrum: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Astra Zeneca: Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Forty Seven Inc: Research Funding; Genentech: Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy, Speakers Bureau. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Hamadani:Otsuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy; Medimmune: Consultancy, Research Funding; Pharmacyclics: Consultancy. Martin:Karyopharm: Consultancy; I-MAB: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Sandoz: Consultancy; Teneobio: Consultancy. Flowers:Pharmacyclics/Janssen: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Millenium/Takeda: Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; BeiGene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Spectrum: Consultancy; Celgene: Consultancy, Research Funding. Kahl:BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy.

Background: In sickle cell anemia, very few markers of disease have been shown to correlate with activity and severity of crisis. We aimed to identify any patterns amongst biomarkers and co-morbidities that correlate with death from multi-organ failure when admitted for sickle cell crisis. Methods: We identified 20 patients with sickle cell anemia who died of multi-organ failure at Grady Memorial Hospital from 2010-2016. We described baseline characteristics, such as hemoglobin phenotype, age, gender as well as features at presentation such as vital signs, laboratory data, clinical signs and symptoms (I.e. worsening pain), and co-morbidities. We examined bivariate associations between clinical characteristics and the length of survival after multi-organ failure. In a secondary analysis, we investigated clinical and demographic features that most accurately predict infection with gram-negative bacteria. To achieve this, we fit a multivariate logistic regression model and perform leave-one-out cross validation to assess the predictive performance of the fitted model on unseen data. Results: At baseline, the average age of a patient is 43.8 years (sd=14.7 years). A majority of our cohort are women (60%), do not smoke (70%), and were not on hydroxyurea (80%). Time to death from multi-organ failure was 3.05 days (95% C.I.: 0.20, 5.90), and only 43% identified having "worsening pain." Among complications, 23% had a stroke and 25% had an infection with gram-negative bacteria. With regards to laboratory data, average WBC was 13.4 (95% C.I.: 11.04, 15.70), Platelets 155 (95% C.I.: 102.22, 208.38), d-dimer 12,892 (95% C.I.: -2498.47, 33437.87) and ferritin 3108 (95% C.I.: 795.07, 5421.63). When using a univariate analysis, we identified that stroke (p=0.008), age (p=0.022) and platelet count at the time of presentation (p=0.039) correlated with time to death. We also identified a statistically significant decrease in the platelet count from baseline to time of multi-organ failure (-105.6, p Conclusion: We have described a cohort of patients with sickle cell anemia who died of multi-organ failure and found that some factors may have correlated with time to death. The most poignant factors include age, platelet count, and drop in platelet count from baseline. It is also interesting that a proportion of these patients developed a gram-negative bacterial infection, which is a common cause of mortality in sepsis. Although our cohort is small, these data may help guide future studies with larger cohorts of patients to identify what puts these patients at risk of death from multi-organ failure. Disclosures No relevant conflicts of interest to declare.

Introduction: Time to treatment (TTT) is an important prognostic factor in patients with newly diagnosed diffuse large B-cell lymphoma (Maurer et al JCO 2018) where patients who initiate therapy quickly after diagnosis have an inferior event free survival compared to those who do not require such immediate treatment initiation. More recently, TTT has shown to be associated with adverse clinical factors and inferior outcomes in mantle cell lymphoma (MCL; Maurer, et al ASH, 2018). However, there is a paucity of data on the impact of TTT on overall survival (OS). We sought to validate these findings and to evaluate the impact of TTT on survival outcomes in newly diagnosed patients with MCL. Methods: We included patients from 12 medical centers in the United States with MCL diagnosed between January 1, 2000, and January 1, 2018, who had information on the TTT and initiated treatment within 60 days of diagnosis (to exclude patients whose treatment was purposefully deferred). TTT was defined as the time in days from first lymphoma diagnosis to initiation of therapy. Patients who received treatment within 14 days were categorized into short TTT group. We compared differences between the two groups (TTT 14 days and ≤ 60 days, longer TTT group) using chi-squared test, Fisher's exact tests, or ANOVA tests as appropriate. OS was defined as the time from diagnosis to death or last follow-up. Patients not experiencing an event were censored at their last known follow-up. OS was determined using the Kaplan-Meier method, and univariable and multivariable models were developed to identify predictors of OS. Results: Of 1,168 patients with newly diagnosed MCL, seven hundred fifty-five patients met the inclusion criteria and were included in this analysis, including 205 (27%) with short TTT and 550 (73%) with longer TTT. Median time to treatment was 7 days (range, 0-14) for the short TTT group vs 31 days for the longer TTT group (range, 15-60 days). The median age for the entire cohort was 63 years, 75% of patients were male, and 93% of patients had ECOG 0-1. The proportion of patients with stage 4 disease (93 vs 86%, p=0.015), elevated LDH (58 vs 39%, p3 cytogenetic abnormalities (29 vs 14%, p=0.005), B symptoms (47 vs 29%, p On univariable analysis, factors associated with inferior OS included, TTT=2 (p10k (p=0.002), BM involvement (p=2 (HR=2.25, 95%CI=1.22-4.14; p=0.009), elevated LDH (HR=1.81, 95%CI=1.16-2.85; p=0.01), and receipt of non-intensive regimen (HR=1.61, 95%CI=1.04-2.50; p=0.03) were significant predictors of OS while B symptoms was not. Conclusions: Short TTT for patients with newly diagnosed MCL is associated with aggressive disease features and inferior OS despite an increased likelihood of receiving intensive induction regimens. Further studies are needed to identify molecular determinants of such aggressive disease behavior that can be assessed quickly and utilized to initiate appropriate therapy in a timely manner. Ongoing front-line clinical trials in MCL should be developed in a way to facilitate enrollment of patients requiring urgent therapy, including potentially permitting a cycle of off-study treatment to manage symptoms while a patient is screened and enrolled. Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Kolla:Amgen: Equity Ownership. Bachanova:GT Biopharma: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Gerson:Seattle Genetics: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Danilov:Bristol-Meyers Squibb: Research Funding; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Genentech: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Hill:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Ghosh:Forty Seven Inc: Research Funding; AbbVie: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Speakers Bureau; Genentech: Research Funding; Spectrum: Consultancy, Speakers Bureau. Park:Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; BMS: Consultancy, Research Funding. Hamadani:Pharmacyclics: Consultancy; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene: Consultancy; Otsuka: Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding. Martin:I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Teneobio: Consultancy. Kahl:AbbVie Inc, Acerta Pharma - A member of the AstraZeneca Group, AstraZeneca Pharmaceuticals LP, BeiGene, Celgene Corporation, Genentech, Pharmacyclics LLC, an AbbVie Company, Roche Laboratories Inc.: Consultancy. Flowers:V Foundation: Research Funding; National Cancer Institute: Research Funding; Millenium/Takeda: Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; Spectrum: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Optimum Rx: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Bayer: Consultancy. Cohen:Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Janssen Pharmaceuticals: Consultancy.

Background and Purpose— Little is known about how regions vary in their use of thrombolysis (intravenous tissue-type plasminogen activator and intra-arterial treatment) for acute stroke. We sought to determine regional variation in thrombolysis treatment and investigate the extent to which regional variation is accounted for by patient demographics, regional factors, and elements of stroke systems of care. Methods— Retrospective cross-sectional study of all fee-for-service Medicare patients with ischemic stroke admitted via the Emergency Department from 2007 to 2010 who were assigned to 1 of 3436 hospital service areas. Multilevel logistic regression was used to estimate regional thrombolysis rates, determine the variation in thrombolysis treatment attributable to the region and estimate thrombolysis treatment rates and disability prevented under varied improvement scenarios. Results— There were 844 241 ischemic stroke admissions of which 3.7% received intravenous tissue-type plasminogen activator and 0.5% received intra-arterial stroke treatment without or without intravenous tissue-type plasminogen activator over the 4-year period. The unadjusted proportion of patients with ischemic stroke who received thrombolysis varied from 9.3% in the highest treatment quintile compared with 0% in the lowest treatment quintile. Measured demographic and stroke system factors were weakly associated with treatment rates. Region accounted for 7% to 8% of the variation in receipt of thrombolysis treatment. If all regions performed at the level of 75th percentile region, ≈7000 additional patients with ischemic stroke would be treated with thrombolysis. Conclusions— There is substantial regional variation in thrombolysis treatment. Future studies to determine features of high-performing thrombolysis treatment regions may identify opportunities to improve thrombolysis rates.