Maurer, Matthew J.

e13569 Background: Progress in understanding the molecular biology of DLBCL has led to development of complex molecular classifications that rely on sequencing methods. These molecular clusters are defined by activation of distinct pathways and may aid in selecting targeted therapy. In the molecular era, tissue requirements in clinical trials have increased to ensure sufficient tissue for molecular testing, potentially resulting in bias for enrollment of patients with larger excisional biopsies (EB). We examined the impact of tissue biopsy method on outcomes of DLBCL in a prospective observational study. Methods: Consecutive adult patients with DLBCL within 9 months from their initial diagnosis were enrolled into the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). Demographics, clinical variables, type of tissue biopsy (EB vs. core needle biopsy (CNB)) for initial diagnosis and initial treatment were recorded at baseline. Pts were contacted every 6 months from the date of diagnosis for first 3 years and then annually thereafter. Study objectives were event free survival (EFS) and overall survival (OS) by tissue biopsy method. Results: A total of 1061 patients with newly diagnosed DLBCL, from 2002 to 2015, were included. The table lists baseline characteristics of the cohort. 593 (56%) pts underwent EB and 468 (44%) underwent CNB for initial diagnosis. A significantly higher proportion of patients receiving CNB had performance status >=2, advanced stage, high risk disease by international prognostic index (IPI), abnormal lactate dehydrogenase. Median time from diagnosis to treatment initiation (DTI) was significantly shorter in the CNB group (13 days) than EB group (19 days). 2-year EFS (60% vs 75%, HR 0.75 (0.6-0.9), p <0.01) was significantly lower in CNB than EB group. There was a trend towards lower OS (75% vs 80%, HR: 0.8 (0.6-0.95), p =0.049) in CNB than EB group. Conclusions: Patients undergoing CNB are more likely to have higher risk disease, shorter DTI and survival compared to those undergoing EB. A need for large amount of diagnostic tissue in biomarker driven clinical trials may result in disproportional exclusion of high risk DLBCL pts who have inferior outcomes after standard treatment and could potentially benefit from novel agents, resulting in overperformance of the control arm. The need for tissue must be carefully balanced against resulting selection bias.[Table: see text]

AbstractThe development of cardiovascular disease (CVD) in long‐term survivors of lymphoma is of increasing importance. Here, we characterize the cumulative incidence and risk factors for CVD in lymphoma patients diagnosed in the current treatment era. From 2002–2015, newly diagnosed lymphoma patients (>18 years) were enrollment into a prospective cohort study that captured incident CVD, consisting of congestive heart failure (CHF), acute coronary syndrome (ACS), valvular heart disease (VHD), and arrhythmia. The cumulative incidence of CVD was calculated with death modeled as a competing risk. We estimated the association of treatment with anthracyclines or radiotherapy and traditional CVD risk factors with incidence of CVD using hazard ratios (HR) and 95% confidence intervals (CI) estimated from Cox regression. After excluding prevalent CVD at lymphoma diagnosis, the study consisted of 3063 patients with a median age of 59 years (range 18–95). The cumulative incidence of CVD at 10‐years was 10.7% (95% CI, 9.5%–12.1%). In multivariable analysis, increasing age (HR = 1.05 per year, p < 0.001), male sex (HR = 1.36, p = 0.02), current smoker (HR = 2.10, p < 0.001), BMI > 30 kg/m2 (HR = 1.45, p = 0.01), and any anthracycline treatment (HR = 1.57, p < 0.001) were all significantly associated with risk of CVD. Anthracyclines were associated with increased risk of CHF (HR = 2.71, p < 0.001) and arrhythmia (HR = 1.61, p < 0.01), but not VHD (HR = 0.84, p = 0.58) or ACS (HR = 1.32, p = 0.24) after adjustment for CVD risk factors. Even in the modern treatment era, CVD remains common in lymphoma survivors and preventive efforts are required that address both treatment and CVD risk factors.

Abstract The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone+rituximab) is often faced by clinicians. We conducted a systematic review assessing the impact of R-CHOP DI on DLBCL survival outcomes, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P) guidelines. We searched MEDLINE, EMBASE, and Cochrane CENTRAL for studies with ≥100 patients treated with R-CHOP/R-CHOP–like therapies published from January 2002 through November 2020. Studies were included if they reported the impact of R-CHOP DI on survival outcomes. We screened records, extracted data, and reviewed all the studies for quality and statistical appraisal. Of 380 screened records, 13 studies including 5188 patients were reviewed. DI was often calculated as the ratio of the cumulative delivered dose of prespecified drug(s) to the cumulative planned dose multiplied by a time-correction factor. Lower DI (intended or relative) was associated with inferior survival in 7 of 9 studies reporting crude survival analyses. Multivariable analysis using DI as a covariate was performed in 10 studies. Six showed an association (P &lt; .05) with adjustment for other covariates, and 4 did not. Most studies and those larger studies of higher quality showed poorer outcomes associated with reduced DI. In subgroups aged ≥80 years, survival was not consistently affected by reduced DI. DI-specific randomized trials are warranted, but these data support full-dose R-CHOP in elderly and fit patients aged &lt;80 years with DLBCL, but not in those aged ≥80 years, where dose-reduced R-CHOP does not appear to compromise survival.

Abstract Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Abstract Background: Most indolent non-Hodgkin lymphomas (NHL) are considered incurable and are characterized by relapse and remission. Quality of life (QOL) can be affected by disease burden, side effects of treatment, and psychosocial effects of living with an incurable cancer. However, little is known about QOL in this population. We sought to describe QOL at diagnosis, change in QOL over time, and determinants of QOL in patients with indolent NHL. Methods: Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource. Eligibility criteria included age ≥18 years; exclusion criteria included HIV-positive, non-US residency, and inability to complete surveys in English. All pathology was reviewed by a hematopathologist. Patients with indolent B-cell NHL were included in this analysis. QOL was measured at baseline (BL) and 3 year follow-up (FU3) with the Functional Assessment of Cancer Therapy-General scale (FACT-G), which measures 4 QOL domains: physical, social/family, emotional, and functional well-being (WB), and a single item Linear Analogue Self-Assessment (LASA) for measuring overall QOL. Patients who did not complete ≥80% of FACT-G questions were excluded. Clinical data were abstracted according to a standard protocol and patients were systematically followed for events (progression, re-treatment, and death). CLL patients were excluded for event analysis due to differing definitions of outcome (progression/retreatment vs. time to first treatment). Treatment was defined as any systemic therapy (including chemotherapy, targeted agents, or antibody therapy) or radiation. QOL scores were transformed to a 0-100 scale with 100 representing the best WB or QOL for analysis. Change in QOL was assessed using the raw difference in QOL scores (i.e., FU3-BL) on the 0-100 scale with positive change scores representing improvements; minimally important difference was defined as 7 points on the transformed FACT-G subscales per previously established cutoffs (Yost and Eton, Eval & Health Prof. 2005 Jun;28:172-91). Changes in QOL from BL to FU3 were assessed using one-sample t-test of change scores vs zero. Results: 1050 patients with indolent NHL enrolled between 9/02-12/2012 and with both pre-treatment and 3 year QOL were included. QOL was collected after initiation of therapy in 215 patients (20%) and prior to therapy in 835 (80%). Subtype was 41% CLL/SLL, 32% grade 1-2 FL, 14% extranodal marginal zone, and 13% other (lymphoplasmacytic lymphoma and other). Median age was 62 years and 55% were male. At the FU3 assessment, 577 patients (55%) had received treatment, 42 (4%) transformed, and 53 (25%) had an event. Emotional WB significantly improved from BL to FU3 (mean +5.9, SD 13.3, p&lt;0.001) while social/family WB significantly decreased (mean -4.8, SD 20.5, p&lt;0.001). Functional WB, physical WB, overall FACT-G, and overall QOL LASA were not significantly different at FU3. These findings were similar in those who were treated vs. those who were observed. We also assessed the results stratified by non-CLL patients who had progression or retreatment between BL and FU3. In patients with an event in the first 3 years, emotional WB had a significant improvement from BL to FU3 (mean +3.6, SD 13.6, p=0.002) and overall QOL LASA decreased (mean -4.0, SD 20.0, p=0.01). In patients without an event, improvements were reported in functional WB (mean +2.1, SD 18.2, p=0.01), physical WB (mean +2.5, SD 13.9, p=0.001), emotional WB (mean +7.0, SD 15.0, p&lt;0.001), and overall QOL LASA (mean +1.1, SD 11.4, p=0.03), while social/family WB decreased (mean -6.2, SD 20.3, p&lt;0.001). Sensitivity analysis showed that results were consistent in the subset of patients who had BL QOL collected prior to initiating therapy. While many changes were statistically significant, they were small in magnitude; only the improvement in emotional WB in the entire cohort approached clinical significance and met that criterion in those without an event. Conclusions: In this large sample of patients with indolent lymphoma, QOL generally remained stable from diagnosis to FU3 while emotional WB showed improvement, suggesting psychosocial adaptation by the patient. Mean score changes in functional WB, physical WB, emotional WB, social/family WB, and overall QOL were more pronounced in patients without an event in the first 3 years since diagnosis. Disclosures Shanafelt: Hospira: Research Funding; AbbVie: Research Funding; Celgene: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Research Funding; Jannsen: Research Funding; Pharmacyclics: Research Funding.

Abstract Introduction: Although increased physical activity (PA) is associated with improved quality of life in cancer survivors, knowledge about the impact of PA on survival in lymphoma patients is limited. We studied the impact of usual adult PA and PA at 3 years after diagnosis on overall (OS) and lymphoma-specific (LSS) survival in lymphoma patients. Methods: Lymphoma patients were prospectively enrolled within 9 months of diagnosis into the Lymphoma SPORE Molecular Epidemiology Resource (MER) cohort. At baseline, patients reported their usual level of mild, moderate and strenuous PA during most of their adult life and (for survivors) again at the 3 year follow-up (FU3), which we used to calculate the Godin Leisure Score Index (LSI). At FU3, patients also self-reported change in PA since diagnosis as increase, decrease or no change. LSI was modeled as a continuous score (per 10-point change) and by tertile. Survival was measured as time from diagnosis (for baseline PA) and time from FU3 (for FU3 PA) until death due to any cause and due to lymphoma. We evaluated the association of PA with outcome using Kaplan-Meier curves as well as hazard ratios (HRs) and 95% confidence intervals (CI) from Cox models stratified by lymphoma subtype and adjusted for age and sex (and baseline PA for change models). Results: Of 4087 patients enrolled in the MER at the Mayo Clinic from 2002-2012, 3129 had baseline PA data (3060 evaluable for LSI), and 1845 (1395 evaluable for LSI) had FU3 PA data. In the baseline cohort, 57.6% of the patients were male. The median age at diagnosis was 62 years (range 18-92 years). The majority had ECOG performance status &lt;2 (95%), no B-symptoms (85.8%) and advanced disease (63% stage III-IV) at diagnosis. The subtypes included were CLL/small lymphocytic (25.9%), follicular (18.1%), diffuse large B-cell (16.8%), marginal zone (8.1%), Hodgkin (6.9%), mantle cell (4.8%), T-cell (5%) and other (14.3%) lymphomas. The median LSI was 28 (range 0-57) at baseline and 25 (range 0-67) at FU3 with a median change in LSI of -2 (range -57 to 61). At a median follow-up of 84 months from diagnosis (IQR 59-119 months) in the cohort with baseline PA, there were 806 total deaths (271 in pts with FU3 PA) and 423 lymphoma deaths (104 in pts with FU3 PA). When analyzed as a continuous variable, baseline LSI was associated with OS (HR 0.95, 95% CI 0.91-0.99) and LSS (HR 0.95, 95% CI 0.90-1.01). LSI by tertiles was associated with OS (p&lt;0.0001, Figure 1a), and patients in the high LSI compared to the low LSI tertile had superior OS (HR 0.81, 95% CI 0.68-0.97) and LSS (HR 0.81, 95% CI 0.63-1.04). For prognosis after 3 years, continuous LSI at FU3 was also associated with superior OS (HR 0.84, 95% CI 0.77-0.92) and LSS (HR 0.76, 95% CI 0.65-0.89). LSI at FU3 by tertiles was associated with OS (p&lt;0.0001, Figure 1b), and patients in the high LSI compared to the low LSI tertile had superior OS (HR 0.51, 95% CI 0.34-0.77) and LSS (HR 0.33, 95% CI 0.16-0.67). A change in LSI from baseline to FU3 PA was associated with superior OS (HR 0.84, 95% CI 0.76-0.92) and LSS (HR 0.74, 95% CI 0.64-0.87) after FU3. Change in LSI by tertiles was associated with OS (p=0.0007, Figure 1c). Compared to patients with stable LSI (change of LSI between -10 and 5 points from baseline, n=429), patients who increased LSI by &gt; 5 (n=464) had improved OS (HR 0.67, 95% CI 0.45-1.00) and LSS (HR 0.47, 95% CI 0.23, 0.94), while patients who decreased LSI by &gt;10 (n=477) had no association with OS or LSS. Self-reported change in PA from baseline to FU3 was associated with OS (p&lt;0.0001, Figure 1d); compared to no change, an increase in PA was not associated with OS (HR 0.79, 95% CI 0.42-1.48) or LSS (OR 0.73, 0.26-2.07), while a reduction in PA was associated with inferior OS (HR 1.94, 95% CI 1.49-2.53) and LSS (HR 2.51, 95% CI 1.62-3.88). After excluding patients with any events through FU3, the associations for the PA change and OS remained significant for change in LSI (HR 0.91, 95%CI 0.83-1.00) and self-reported decrease in PA (HR 1.83, 95%CI 1.32-2.53). Conclusions: Patients with a higher level of usual PA during adult life have significantly better OS and LSS after lymphoma diagnosis compared to those who are less physically active. Higher PA in 3-year survivors is also associated with improved survival, while a reduction in physical activity is associated with worse outcomes. These data support an important role for PA in lymphoma survivorship and also provide a strong rationale for a PA intervention trial in lymphoma patients. Figure 1 Figure 1. Disclosures Cohen: LAM Therapeutics, Inc: Research Funding; Takada: Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bioinvent: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees. Flowers: Spectrum: Consultancy; OptumRx: Consultancy; Acerta: Research Funding; Onyx: Research Funding; Janssen Pharmaceutical: Research Funding; V Foundation: Research Funding; TG Therapeutics: Research Funding; National Cancer Institute: Research Funding; Burroughs Welcome Fund: Research Funding; Genentech/Roche: Consultancy, Research Funding; Gilead: Consultancy; Research to Practice: Research Funding; Millennium/Takeda: Research Funding; National Institutes Of Health: Research Funding; Prime Oncology: Research Funding; Educational Concepts: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Seattle Genetics: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Celgene: Consultancy, Research Funding; Infinity: Research Funding; Bayer: Consultancy; Clinical Care Options: Research Funding. Cerhan: Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering .

Abstract Introduction: Recent results from two independent patient series have shown that chromosomal rearrangements of DUSP22 (DUSP22r+) and TP63 (TP63r+) can predict outcome in ALK-negative anaplastic large cell lymphoma (ALK-ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) with morphologic features resembling ALK-ALCL (Parilla-Castellar E, Blood 2014; Pedersen MB, Blood 2017). While DUSP22r+ is predictive for excellent survival similar to that of ALK+ALCL after CHOP/CHOP-like therapy, the rarely occurring TP63r+ is associated with an aggressive clinical behavior and poor outcome. The largest subgroup, i.e. patients with neither ALK nor DUSP22 nor TP63 rearrangements (triple negative), show a 5 year (yr) overall survival (OS) intermediate between that of ALK-/DUSP22r+ and ALK-/TP63r+ patients. The aim of the present study was to assess the impact of upfront high-dose therapy with autologous stem cell transplant (HDT/ASCT) on outcome in adult ALCL and PTCL-NOS patients according to their ALK, DUSP22 and TP63 status. The survival results from the two published series were pooled with those of a Nordic Lymphoma Group trial, the NLG-T-01 (d'Amore et al, JCO 2012), where patients were treated with 1st line CHOEP/CHOP followed, in chemosensitive cases, by upfront HDT/ASCT. Methods: Fluorescence in situ hybridization was performed on sections of previously constructed tissue microarrays using break-apart probes for the DUSP22-IRF4 and TP63 loci and a dual-fusion probe for TBL1XR1/TP63 fusion [inv(3)(q26q28)]. Evaluation of DUSP22 and TP63 rearrangements was performed in a blinded fashion without knowledge of PTCL subtype, clinical course, or outcome. Three independent patient cohorts were included: (i) one from Mayo Clinic consisting of 31 DUSP22r-, ALK-ALCL and PTCL-NOS (triple negative: 25; TP63r+: 6); (ii) one from Denmark consisting of 93 DUSP22r-, ALK-ALCL and PTCL-NOS (triple negative: 90; TP63r+: 3); and one from the NLG-T-01 trial consisting of 46 ALK-ALCL and PTCL-NOS (triple negative: 37; TP63r+: 1; DUSP22r+: 8), leading to a total study population of 170 patients. ALK+ ALCL was not included in the analysis, since no patients with this histology entered the NLG-T-01 trial. Association of genetic subtype with OS was assessed using Kaplan-Meier curves and Cox proportional models for hazard rate ratios (HR). Significant differences were defined as P &lt;0.05. Results: The eight DUSP22r+ patients (7 ALK-ALCL and 1 PTCL-NOS) from NLG-T-01 had a 5-yr OS of 83%, (95%CI 27-97), similar to that reported for DUSP22r+ in the Mayo and Danish cohorts (90% and 80%, respectively). No lymphoma-related events were observed in this subset. The only event was a septic death due to HDT-induced cytopenias in a patient who was in complete remission (CR). Among the 162 patients with DUSP22r-, ALK-ALCL and PTCL-NOS, those consolidated with HDT/ASCT (n=47) had a significantly better outcome (5-yr OS: 45%) than those treated with induction chemotherapy alone (5-yr OS: 30%) (n=115) (P=0.01). The patients in the HDT/ASCT group were younger (P&lt;0.001) and had more advanced stage disease (P=0.002). The improvement in OS persisted when the analysis was limited to transplant eligible patients and adjusted for age and stage (HR 0.52 95%CI 29-91, P=0.023) or International Prognostic Index (IPI) groups (HR 0.49, 95%CI 20-82, P=0.006). Of the 10 TP63r+ patients found within the pooled cohort, 6 were transplant eligible. Of these, 5 were not transplanted (intention-to-treat) while one was (Nordic trial). The latter patient achieved a still ongoing long-term CR, while all others died of lymphoma progression. Conclusion: In ALK-ALCL and PTCL-NOS patients from the NLG-T-01 trial, DUSP22r+ was associated with a very good outcome, similar to that seen in DUSP22r+ patients who had not undergone upfront autologous transplant. This observation supports the impression that upfront HDT/ASCT may not be of benefit in these patients. TP63r+ predicted poor outcome in non-transplanted patients. The impact of HDT/ASCT in the TP63r+ setting could not be adequately evaluated, since only one patient from the NLG-T-01 trial cohort was found to be TP63r+. Notably, this patient was the only survivor of the TP63r+ subset. For DUSP22r-, ALK-ALCL and PTCL-NOS patients taken as one group, those who received upfront HDT/ASCT had a superior survival compared to their age- and IPI-matched non-transplanted counterparts. Disclosures Ellin: ROCHE: Consultancy, Research Funding; CTI: Consultancy. Mannisto: Roche: Honoraria, Other: Travel expence; Takeda: Honoraria, Other: Travel expence; Amgen: Other: Travel expence; Novartis: Other: Travel expence; Celgene: Other: Travel expence; Gilead: Other: Travel expence; Pfizer: Honoraria; SOBI: Honoraria. Cerhan: Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering . Toldbod: Takeda Pharma: Honoraria.

Abstract Disease progression after frontline therapy for Diffuse large B‐cell lymphoma (DLBCL) is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (SEAL) consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time‐dependent concordance indices (c‐statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post‐progression OS (both p < 0.001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c = 0.64, MER c = 0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post‐progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CAR‐T therapy as well as trial designs. The model is available in smartphone‐based point of care applications.

Background: Obesity is increasing worldwide, with the highest prevalence in the United States. High or low body mass index (BMI) is a well-established risk factor for increased all-cause mortality and also has been associated with cancer-specific mortality. However, the impact of BMI on survival following diagnosis with lymphoma currently remains controversial. We leveraged a prospective cohort of lymphoma patients to assess the relationship of BMI two years prior to diagnosis (BMI-2), at diagnosis (BMI-dx), and three-years post-diagnosis (BMI+3) with lymphoma-specific survival (LSS) as the primary endpoint and with event-free survival (EFS) and overall survival (OS) as secondary endpoints. Patient and Method: Patients were prospectively enrolled at lymphoma diagnosis to the SPORE Molecular Epidemiology Resource (MER) cohort at Mayo Clinic and University of Iowa from 2002-2015. BMI-2 and BMI+3 were self-reported in patient questionnaires, while BMI-dx was extracted from the medical chart. Patients with extreme BMI (BMI &lt;14 and BMI ≥50) were excluded from the analysis. BMI change from BMI-2 to BMI-dx and from BMI-dx to BMI+3 was categorized as no change (-5% to 5%), decrease (&gt;-5%), and increase (&gt;+5%). Person-time at risk was assessed from lymphoma diagnosis until death or last follow-up, except for analyses of BMI change from BMI-dx to BMI+3, which started person-time at risk when the 3-year (+/- 6 months) follow-up questionnaire was returned. Cause of death was assigned by a study clinician. For all lymphoma patients combined and in the most common subtypes, we evaluated the association of BMI at each time point and change in BMI with EFS, LSS, and OS using hazard ratios (HRs) and 95% confidence intervals (CI) from multivariable adjusted Cox models. Results: A total of 4,009 lymphoma patients (including 670 diffuse large B-cell lymphoma [DLBCL], 689 follicular lymphoma [FL] and 1018 chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] and 1,632 others) with data on BMI-dx were included. Among them, 2,955 patients had BMI-2 and 2,004 had BMI+3 and were evaluable for change in BMI. The median age of all patients at diagnosis was 61 years (range 18-92 years), and 94% of patients had ECOG performance status &lt;2. At the time of diagnosis, 28% were normal weight (BMI 18.5-25), 1% were underweight (BMI &lt;18.5), 39% were overweight (BMI 25-30) and 32% were obese (BMI ≥30). With a median follow-up of 108 months from diagnosis (IQR 83-143 months), 1320 deaths were observed, 48% of which were due to lymphoma. Patients with FL who were obese at BMI-2 had significantly shorter LSS (HR: 3.02, 95%CI: 1.43-6.41, p=0.004). Associations between obesity at BMI-2 and LSS were not evident for DLBCL (HR: 1.04, 95%CI: 0.62-1.76, p=0.879) or CLL/SLL (HR: 1.10, 95%CI: 0.71-1.70, p=0.668) (Table). BMI-dx was not associated with LSS in any lymphoma patients, except that DLBCL patients who were underweight at BMI-dx (n=10) experienced shorter LSS (HR: 3.52, 95%CI: 1.22-10.1, p=0.020). This correlated significantly with presence of B symptoms (p=0.004) and may signify aggressive disease. Across all subtypes, &gt;5% decrease in BMI from BMI-2 to BMI-dx was associated with significantly shorter LSS in patients with (HR: 2.02, 95%CI: 1.65-2.48, p&lt;0.001). However, only for FL patients, &gt;5% increase in BMI from BMI-dx to BMI+3 also was associated with significantly shorter LSS in subsequent years (HR: 3.74, 95%CI: 1.30-10.8, p=0.014). The associations reported for LSS generally were similar for EFS and OS. Conclusions: FL patients with obesity prior to diagnosis or who experienced increasing BMI after the diagnosis had significantly shorter LSS. The impact of weight control after the diagnosis of FL patient outcomes warrants investigation. Figure Disclosures Maurer: Celgene / BMS: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Flowers:Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; Kite: Research Funding; Bayer: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; National Cancer Institute: Research Funding; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; BMS/Celgene: Research Funding.