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PURPOSE: Patients' concerns regarding clinical trial (CT) participation include apprehension about side effects, quality of life (QoL), financial burden, and quality of care. METHODS: We prospectively evaluated the experience of patients with multiple myeloma or lymphoma who were treated on CTs (CT group, n = 35) versus patients treated with standard approaches (non-CT group, n = 88) focusing on QoL, financial burden of care, and patients' perception of quality of care over a 1-year period. RESULTS: There were no significant differences in any of the patient-reported outcomes in CT versus non-CT groups. We observed an initial decline in overall QoL in the first 3 months across both groups, driven primarily by physical and functional well-being. QoL gradually improved and was above baseline by month 12. Patients reported highest improvement in the functional well-being subdomain. Patients in both groups reported high satisfaction with the quality of care received, and there were no differences in overall satisfaction, communication with team, or access to care. At baseline, 16%-19% of patients reported financial burden, which increased to a peak of 33% in the CT group and to 49% in the non-CT group over the course of 1 year. There was no significant difference in financial burden in the two groups overall. Most of the patients reported getting all the care that was deemed medically necessary in both groups. However, a significant proportion of patients reported having to make other kinds of financial sacrifices because of their cancer (CT group: 33% of patients at baseline and 21%-40% over 1 year; non-CT group: 19% at baseline and 25%-36% over 1 year). CONCLUSION: Patients treated on CTs reported comparable QoL and quality of care with the non-CT group. A high proportion of patients reported financial burden over time in both groups. Our findings can serve as a guide to educate patients regarding CT participation and highlight the need to address the significant financial burden experienced by patients with cancer.

PURPOSE: Compliance with US Preventive Services Task Force (USPSTF) age-appropriate cancer screening and immunization guidelines in lymphoma survivors is not known. We sought to measure compliance in non-Hodgkin lymphoma (NHL) survivors and identify any differences based on patient, disease and treatment characteristics. METHODS: Eligible NHL survivors were identified from the Molecular Epidemiology Resource (MER) prospective cohort study. Survivors self-reported colorectal, breast, and prostate cancer screening and influenza immunization in a questionnaire 3-years post-diagnosis (FU3). The USPSTF guidelines were used to define compliance. Chi-square tests were used to compare characteristics of compliant vs non-compliant survivors. RESULTS: 1833 MER participants from 2005-2012 completed a FU3. Rates of breast and prostate cancer screening were 96% and 72%, respectively. No differences in compliance based on patient or disease characteristics or treatment were observed. 92% of survivors were compliant with colorectal cancer screening. Older age, indolent lymphoma histology, and 2008-2012 year of diagnosis were associated with higher compliance. 82% of survivors were compliant with influenza vaccination and older age was associated with higher compliance. CONCLUSION: NHL survivors have high compliance with USPSTF recommendations for cancer screening and immunization. Survivors who are younger or have aggressive lymphomas are less likely to meet the colorectal cancer screening guidelines. Older survivors are more likely to receive influenza vaccination. IMPLICATIONS FOR CANCER SURVIVORS: Measures to further improve preventive care for NHL survivors, especially those younger in age, are necessary.

Mass-spectrometry (MS) assays detect lower levels of monoclonal proteins and result in earlier detection of monoclonal gammopathy of undetermined significance (MGUS). We examined heavy chain MGUS prevalence using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS among 3 risk groups, ages 50 or older: 327 African Americans (AA) and 1223 European Americans (EA) from a clinical biobank and 1093 unaffected first-degree relatives (FDR) of patients with hematologic disorders. Age- and sex-adjusted prevalence rates were directly standardized to 2010 United States population. Prevalence ratios were estimated for comparisons of AA and FDR to the EA group using the Poisson distribution. Results were also compared with population-based prevalence using conventional gel-based methods. Risk groups had similar sex and age distributions. MALDI-TOF MGUS prevalence was higher in the AA (16.5% [95% confidence interval (CI), 12.2%, 20.8%]) and FDR (18.3% [95% CI, 16.6%, 21.6%]) than in EA (10.8% [95% CI, 8.8%, 12.7%]), translating to prevalence ratios of 1.73 (95% CI, 1.31, 2.29) and 1.90 (95% CI, 1.55, 2.34), respectively. MALDI-TOF EA prevalence was over threefold higher than conventional estimates but showed similar age trends. Thus, the MALDI-TOF assay found greater numbers with MGUS but similar relative differences by race, family history, and age as prior studies.

Because there have been a dvances in frontline treatment for mantle cell lymphoma (MCL) over the last 2 decades, we sought to characterize the changes in frontline treatment patterns and their association with outcomes. Patients with newly diagnosed MCL from September 2002 through June 2015 were enrolled in a prospective cohort study, and clinical characteristics, treatment, and clinical outcomes were compared between patients diagnosed from 2002 to 2009 (Era 1) compared with 2010 to 2015 (Era 2). Patient age, sex, and simplified MCL International Prognostic Index (sMIPI) score were similar between the 2 groups. In patients age 65 years or younger, there was less use of rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-Hyper-CVAD) (16.1% vs 8.8%) but more use of rituximab plus maximum-strength cyclophosphamide, doxorubicin, vincristine, and prednisone (R-maxi-CHOP) alternating with rituximab plus high-dose cytarabine (R-HiDAC), also known as the Nordic regimen, and R-CHOP alternating with rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) (1.1% vs 26.4%) and less use of R-CHOP or R-CHOP-like regimens (64.5% vs 35.2%) but more use of R-bendamustine (0% vs 12.1%) in Era 2 (P < .001). These changes were associated with improved event-free survival (EFS; 5-year EFS, 34.3% vs 50.0%; P = .010) and overall survival (OS; 5-year OS, 68.8% vs 81.6%; P = .017) in Era 2. In patients older than age 65 years, there was less use of R-CHOP or R-CHOP-like therapy (39.0% vs 14.3%) and nonstandard systemic therapy (36.6% vs 13.0%) but more use of R-bendamustine (0% vs 49.4%). These changes were associated with a trend for improved EFS (5-year EFS, 25.4% vs 37.5%; P = .051) in Era 2. The shift from R-CHOP or R-CHOP-like regimens to R-bendamustine was associated with improved EFS (5-year EFS, 25.0% vs 44.6%; P = .008) in Era 2. Results from this prospective cohort study provide critical real-world evidence for improved outcomes with evolving frontline patterns of care in patients with MCL.

The 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 3,063 patients with a median age of 59 years (range 18–95) were included. 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, P30 kg/m(2) (HR=1.45, P=0.01), and any anthracycline treatment (HR=1.57, P

The diabetes mellitus (DM) drug metformin targets mechanistic/mammalian target of rapamycin and inhibits lymphoma growth in vitro. We investigated whether metformin affected outcomes of newly diagnosed diffuse large B-cell (DLBCL, n = 869) and follicular lymphoma (FL, n = 895) patients enrolled in the Mayo component of the Molecular Epidemiology Resource cohort study between 2002 and 2015. Hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, sex, body mass index, prognostic index and treatment were used to estimate the association of metformin exposure (No DM/No metformin; DM/No metformin; DM/Metformin) with event-free (EFS), lymphoma-specific (LSS) and overall (OS) survival. Compared to No DM/No metformin DLBCL patients, there was no association of DM/Metformin (n = 48; HR = 1·05, 95% CI 0·59-1·89) or DM/No metformin(n = 54; HR = 1·41, 95% CI 0·88-2·26) with EFS; results were similar for LSS and OS. Compared to No DM/No metformin FL patients, there was no association of DM/Metformin (n = 37; HR = 1·16, 95% CI 0·71-1·89) or DM/No metformin (n = 19; HR = 1·16, 95% CI 0·66-2·04) with EFS; results were similar for LSS. However, DM/Metformin was associated with inferior OS (HR = 2·17; 95% CI 1·19-3·95) compared to No DM/No metformin. In conclusion, we found no evidence that metformin use was associated with improved outcomes in newly diagnosed DLBCL and FL.

The impact of change in health behaviors [physical activity (PA), alcohol and smoking] on quality of life (QOL) in lymphoma survivors is not well understood. We evaluated the associations of health behaviors with QOL domains at diagnosis and at 3-year follow-up (FU3) in 2805 lymphoma survivors. We report clinically significant QOL score differences, defined as scores that exceeded a minimally important difference threshold and were statistically significant. Current smoking was associated with lower QOL at baseline (p

Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosis-to-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States. Validation of results was performed in an independent, clinical trial-based cohort from Europe. Patients and Methods Patients were prospectively enrolled in the University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource (MER; N = 986) or the Lymphoma Study Association (LYSA) LNH-2003 clinical trials program (N = 1,444). All patients received anthracycline-based immunochemotherapy at initial diagnosis. Associations of DTI with clinical factors and outcome were examined. Outcome was assessed using event-free survival at 24 months from diagnosis (EFS24). Results Median (range) DTI was 15 days (0 to 155 days in the MER and 23 days (0 to 215 days) in LYSA. Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B symptoms, and higher International Prognostic Index in both cohorts (all P < .001). Longer DTI was associated with improved EFS24 in both the MER (per-week odds ratio, 0.80; 95% CI, 0.74 to .0.87) and LYSA (per-week odds ratio, 0.90; 95% CI, 0.86 to 0.94); association with EFS24 remained significant after adjustment for International Prognostic Index. Conclusion DTI is strongly associated with prognostic clinical factors and outcome in newly diagnosed DLBCL. DTI should be reported in all clinical trials of newly diagnosed DLBCL and future trials should take steps to avoid selection bias due to treatment delay.

Introduction: TP53 aberrations, including mutations and deletion of 17p (del17p), are important adverse prognostic markers in chronic lymphocytic leukemia (CLL). Prevalence of TP53 aberrations ranges from 7-11% in untreated CLL and increases with disease progression and treatment. Among CLL patients with TP53 aberrations, co-occurrence of TP53 mutations with del(17p) is common. CLL patients with TP53 mutations or del(17p) have significantly worse outcomes when compared to wild-type patients. Previous studies, focusing on CLL patients at time of treatment, are mixed as to whether a single or more than one TP53 aberration impacts outcomes. TP53 is less well studied in monoclonal B-cell lymphocytosis (MBL), an asymptomatic pre-malignant state of CLL. Del(17p) occurs in 3-4% of MBL individuals, and a study of 54 MBL individuals reported a 2% mutation frequency in TP53. Here we estimated prevalence and evaluated the impact of TP53 aberrations in a large cohort MBL or untreated CLL individuals. Methods : Patients with CLL or MBL diagnosed between 2000 and 2019 from the Mayo Clinic CLL Resource with pre-treatment peripheral blood mononuclear cells (PBMC) collected within two years of diagnosis were considered. DNA was extracted from PBMCs with purity >80% or with sorted CD5+/CD19+ clonal cells. The entire coding regions of 59 CLL driver genes were paired end sequenced. Median coverage depth was >1000x per nucleotide, allowing for detection of mutations with variant allelic fraction (VAF) as low as 1%. Somatic mutations were called using MuTect2 in tumor-only mode, and high impact mutations (frameshift, nonsense, and splicing variants) and missense mutations in CLL hot spots were selected. Somatic mutations and FISH del(17p) were used to define TP53 state for each patient: 1) wild-type [no TP53 mutations and normal del(17p)], 2) single-hit [one TP53 mutation or del(17p)], or 3) multi-hit [multiple TP53 mutations or TP53 mutation and del(17p)]. Time to first treatment (TTFT) and overall survival (OS) were analyzed by TP53 state. TTFT and OS were defined as time from sample collection to first treatment or death, respectively, or last follow-up date. Median TTFT and OS was estimated by the Kaplan-Meier method. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for TTFT and OS associations. The models were adjusted for known adverse prognostic factors including clinical diagnosis (CLL or MBL), age at diagnosis, Rai stage, b2 microglobulin, and IGHV mutation status. Results: Individuals with CLL (N=597) or MBL (N=285) were analyzed for prevalence of TP53 mutations and del(17p). We found 58 CLL patients (9.7%) and 15 MBL individuals (5.3%) had TP53 mutations. The median VAF in CLL was 30.9% ( Patients with any TP53 aberration had shorter TTFT than wild-type patients (median 2.3 vs 9.4 years). Among patients with TP53 aberrations, median TTFT was shorter in multi-hit patients (20 events, 1.8 years) compared to single-hit patients (24 events, 3.2 years) (Fig. 1b). In Cox regression, single-hit (HR = 1.7 [1.1-2.6]) and multi-hit (HR = 1.8 [1.1-2.9]) patients had shorter TTFT compared to wild-type patients after adjusting for covariates (Fig. 1c). Multi-hit patients also had shorter OS compared to wild-type patients, while OS in single-hit patients did not significantly differ from wild-type patients (Fig. 1d). Median OS was 5.5 years in multi-hit patients (22 deaths) compared to 15.1 years in wild-type patients (196 deaths) and 14.3 years in single-hit patients (15 deaths). In the OS model adjusted for covariates, multi-hit patients had a significant increased risk (HR = 2.6 [1.6-4.1]), but single-hit patients did not (HR = 1.4 [0.8-2.5]) compared with wild-type patients (Fig. 1e). OS HRs remained stable after censoring at time of treatment. Both TTFT and OS HRs were consistent when mutations with VAF < 10% were excluded. Conclusions: This study suggests single versus multi-hit TP53 aberrations may be important for prognostic outcomes in untreated CLL and MBL patients. Prognostic metrics may need to consider single versus multi-hit TP53 aberrations and include TP53 mutations with low VAF. Figure 1 Figure 1. Disclosures Cerhan: Regeneron Genetics Center: Other: Research Collaboration; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; NanoString: Research Funding; Genentech: Research Funding. Parikh: Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding; Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees. Kay: MEI Pharma: Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolero Pharmaceuticals: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees.

Chronic lymphocytic leukemia (CLL) is a neoplastic disease of mature B-cells with a highly heterogeneous clinical course. While European ancestry (EA) populations present an increased incidence of CLL, African ancestry (AA) populations have a younger median age of onset, higher frequency of adverse prognostic factors, and inferior clinical outcomes. Despite the considerable effort to characterize the genetic landscape of CLL, AA are overwhelmingly underrepresented. Our hypothesis is that the clinical differences observed between AA and EA populations are, in part, explained by underlying genetic features. To address this imbalance, we identified 90 AA patients diagnosed with CLL, 64% of which were untreated at sample collection. RNA and DNA were extracted from CD5+/CD19+ clonal B-cells. We performed mRNA-seq and targeted sequencing in 59 recurrently mutated somatic CLL driver genes. Differentially expressed genes were identified using edgeR. Data was compared to our previously analyzed EA CLL cohort (N=445). The median age at diagnosis was 59 years for AA and 66 for EA and 74% of AA and 50% of EA had unmutated IGHV (u-IGHV) status. When evaluating the entire AA and EA cohorts, there was a significant increased frequency of mutations in TP53, SF3B1, and NFKBIE, identified in 29%, 24%, and 20% of AA CLLs, compared to 5%, 9%, and 9%, respectively, in EA CLLs (p Citation Format: Cecilia Bonolo de Campos, Daniel R. O'Brien, Chantal E. McCabe, Huihuang Yan, Geffen Kleinstern, Zhiquan Wang, Laura A. Bruins, Cristine Allmer, Nicholas J. Boddicker, Charla R. Secreto, Aaron D. Norman, Shulan Tian, Kari G. Rabe, Timothy G. Call, Sameer A. Parikh, Jose F. Leis, Wei Ding, Richard Furman, J Brice Weinberg, James R. Cerhan, Celine M. Vachon, Neil E. Kay, Susan L. Slager, Esteban Braggio. Characterization of underlying genomic features among African ancestry populations diagnosed with chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2209.

Clinical practice guidelines recommend that individuals with HC MBL are evaluated annually for evidence of progression as it has been shown that they progress to develop CLL requiring therapy at a rate of 1-5%/year. Next-generation sequencing identified 59 genes recurrently mutated in CLL, and we previously showed that the tumor mutational load (TML), i.e., the total number of these genes mutated, is associated with a shorter time to first treatment (TTT) among 112 HC MBLs independent of the CLL international prognostic index (CLL-IPI), an established prognostic score. Herein, we continue to support our finding in additional HC MBLs and report the pooled results across the two cohorts. From the Mayo Clinic CLL Resource, we sequenced a total 167 HC MBL (112 from the initial round and 55 from additional sequencing). We extracted DNA from CD5+/CD19+ B-cells and sequenced the coding regions of 59 driver genes. Somatic mutations were called using MuTect2 in tumor-only mode. Germline variants were eliminated based on minor allele frequencies >0.01% and by those identified in public databases, unless present in known CLL mutation hotspots. After filtering, we computed the TML based on the number of genes with high impact (nonsense, frameshift and splicing) and hotspot mutations. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusted for sex and CLL-IPI. Stratified analyses were conducted by low/intermediate risk and high/very high CLL-IPI. Of the 167 HC MBL, low risk CLL-IPI comprised 60%, intermediate risk 28%, high risk 12%; and none were very-high risk. The most commonly mutated genes were SF3B1 (11%), NOTCH1 (9%), TP53 (7%), BIRC3 (7%), and MYD88 (6%); and 52 (31%) individuals had mutations in at least one gene. The median follow-up was 4.4 years, and 26 of the 167 individuals progressed to CLL requiring therapy. HC MBL with ≥2 mutated genes had a 28% 5-year risk of needing therapy compared to 6% among those with no mutated genes. Similar to our initial finding (HR=1.53, CI:1.12-2.07; P=0.007), we found a shorter TTT in the additional HC MBLs (HR=4.63, CI:1.57-13.7, P=0.006), and in the pooled cohort (HR=1.72; CI:1.29-2.28, P=0.0002). When we stratified by CLL-IPI risk, TML remained associated with TTT among individuals with low/intermediate CLL-IPI risk in the additional HC MBLs (HR=3.52, CI:1.11-11.2, P=0.03) and in the pooled cohort (HR=2.25, CI:1.34-3.77, P=0.002). A non-significant 2.8 fold association was observed with high risk CLL-IPI in the pooled cohort. In conclusion, the TML along with the CLL-IPI provide clinicians with a more accurate prognostic information regarding disease progression requiring therapy, especially for those MBLs with low to intermediate risk based on CLL-IPI. If validated, these findings may modify current practice guidelines for individuals with HC MBL. Citation Format: Geffen Kleinstern, Cecilia Bonolo de Campos, Nicholas J. Boddicker, Daniel R. O'Brien, Shulan Tian, Chantel Barney, Kari G. Rabe, Cristine Allmer, Laura Bruins, Aaron D. Norman, Timothy G. Call, Sameer A. Parikh, Jose F. Leis, Wei Ding, Huihuang Yan, James R. Cerhan, Neil E. Kay, Celine Vachon, Esteban Braggio, Susan L. Slager. Tumor mutational load derived from recurrently mutated genes in chronic lymphocytic leukemia (CLL) predicts time-to-first treatment in high-count monoclonal B-cell lymphocytosis (HC MBL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 884.

Introduction Monoclonal gammopathy of undetermined significant (MGUS) is a premalignant plasma cell disorder that is common in individuals over age 50. MGUS prevalence estimates to date have generally been based on results of serum electrophoresis and immunofixation (for heavy chain [HC] MGUS) and additionally, free light chain (for light chain [LC] MGUS). Mass-spectrometry assays, however, can detect lower levels of monoclonal (M) proteins, identify the isotype and provide accurate quantification of the M-protein. Given the evidence that MGUS is likely present at least 10 years prior to its detection, mass spectrometry may provide more accurate estimates of underlying MGUS. We examined the prevalence of HC-MGUS using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry among three risk groups: European Americans (EA), African Americans (AA) and first-degree relatives (FDR) of patients with multiple myeloma (MM), MGUS, chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL). Methods We sampled all AA and a random sample of EA participants ages 50 and older enrolled in the Mayo Clinic Biobank. We also selected unaffected first-degree relatives (limiting to ages 50 and older) from our ongoing family study of hematological malignancies. We screened serum samples by the MALDI-TOF mass spectrometry assay, which is clinically used at Mayo Clinic (known as MASS-FIX) for detection and isotypes of M-proteins. The assay uses isotype-specific nanobody enrichment coupled to MALDI-TOF mass spectrometry. For each of the risk groups, HC- MGUS prevalence was estimated by age (50-59, 60-69, 70+). Age- and sex-adjusted prevalence rates were calculated by direct standardization to the 2010 US population. Ninety-five percent confidence intervals (95% CI) for the prevalence rates and comparisons across the three groups were based on the Poisson distribution. Because free LC information was unavailable, LC-MGUS was not estimated. Results A total 327 AA, 854 EA and 792 FDR were screened for M-proteins using the MASS-FIX assay. All three groups had similar sex (42-44% male) and age distributions (mean[SD] age was 64.5[9.5] yrs., 64.4[8.8] yrs. and 64.9[10.5] yrs. for AA, EA and FDR, respectively). As previously noted using conventional detection methods, the overall prevalence of HC-MGUS was higher in the AA population (16.5% [95%CI: 12.2%, 20.8%]) and FDR (21.5% [95%CI: 18.3%, 24.7%]) than in EA (11.2% [95%CI: 8.8%, 13.5%]), both p-values Conclusion We provided some of the first data on prevalence of HC-MGUS across three risk groups, using a sensitive method for detecting monoclonal proteins. The MASS-FIX assay resulted in substantially higher absolute rates of HC-MGUS (at least 3-fold higher) relative to conventional methods. Further, the prevalence of HC-MGUS among the AA and FDR was significantly higher than the EA population. Thus, the more sensitive assay identified greater absolute numbers of individuals with MGUS, but resulted in similar relationships as seen in prior studies across these risk groups. Our results have implications for future studies of the etiology of MGUS and its progression. Disclosures Dispenzieri: Janssen: Research Funding; Pfizer: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Celgene: Research Funding; Takeda: Research Funding. Kumar:Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Karyopharm: Consultancy; Genecentrix: Consultancy; Cellectar: Other; Carsgen: Other, Research Funding; Merck: Consultancy, Research Funding; Dr. Reddy's Laboratories: Honoraria; Adaptive Biotechnologies: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Sanofi: Research Funding; MedImmune: Research Funding; Novartis: Research Funding. Murray:The Binding Site: Patents & Royalties: Patent Use of Mass Spec to identify monoclonal proteins licensed to The Binding Site.

Background Performance status (PS) is a measurement of a patient’s functional capabilities and has been validated as a prognostic indicator in patients with cancer. This study was conducted to compare patient and physician-rated Eastern Cooperative Oncology Group (ECOG) PS to determine the incidence of inter-observer variability and identify determinants of PS disagreement among a cohort of patients with hematologic malignancy. Methods Newly diagnosed patients with leukemia and lymphoma were prospectively enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) from 2002-2008. At diagnosis, patients and their physicians were asked to independently rate ECOG PS. Those who reported PS within 1 month of diagnosis were included in this analysis. Chi-squared and Wilcoxon rank-sum tests were used to assess the association between PS disagreement and prognostic or demographic factors; Cox proportional hazards models and c-statistics were used to evaluate the association between PS and overall survival. Results 1269 patients were included with a median age of 61 years (range 18-91). Of these, 58% were male; 275 had chronic lymphocytic leukemia (CLL), 127 had Hodgkin lymphoma (HL), and 867 had non-Hodgkin lymphoma (NHL). Overall, 829 (65%) patients and physicians rated PS the same. Age greater than 60 was a significant predictor of disagreement overall (p Patient and physician-rated PS were both significant predictors of overall survival in univariate models and also adjusted for subtype and subtype specific risk score. The prognostic ability for PS was similar for both patient rated and physician-rated assessment overall (c-statistic=0.76 for both patient and physician rated PS) and in those with HL (c-statistic=0.85 for both patient and physician rated PS) and NHL (c-statistic=0.76 for both patient and physician rated PS). However, patient-rated PS was better for prognostication in CLL (c-statistic=0.75; p Conclusions Patients with hematological malignancies and their physicians do not always rate PS the same, particularly in patients who are older or have more advanced or aggressive disease. These findings suggest the need for physicians to communicate with patients when determining PS, as PS is a strong predictor of survival. Disclosures: No relevant conflicts of interest to declare.

PURPOSE In patients with diffuse large B-cell lymphoma (DLBCL), most relapses occur within the first 2 years of diagnosis. We sought to define the rate and outcome of late relapses that occurred after achieving event-free survival at 24 months (EFS24). METHODS We prospectively followed 1,324 patients with newly diagnosed DLBCL from 2002 to 2015 and treated with immunochemotherapy. Cumulative incidences of late DLBCL and indolent lymphoma relapses were analyzed as competing events. Postrelapse survival was defined as time from first relapse to death from any cause. RESULTS In 847 patients who achieved EFS24, the cumulative incidence of late relapse was 6.9% at 3 years, 9.3% at 5 years, and 10.3% at 8 years after EFS24. The incidence of DLBCL relapse was similar in patients with DLBCL alone at diagnosis (6.3% at 5 years), compared with patients with concurrent indolent lymphoma at diagnosis (5.2%; P = .46). However, the rate of indolent lymphoma relapse was higher in patients with concurrent indolent lymphoma (7.4% v 2.1% at 5 years; P < .01). In patients with DLBCL alone, the rate of DLBCL relapse was similar in the germinal center B-cell–like (GCB) (4.1% at 5 years) and non-GCB (4.0%; P = .71) subtypes, whereas the rate of indolent lymphoma relapse was higher in patients with the GCB subtype (3.9% v 0.0% at 5 years; P = .02). Postrelapse survival was inferior for patients who relapsed with DLBCL than for those who relapsed with indolent lymphoma (median 29.9 months v unreached; P < .01). CONCLUSION Patients with DLBCL with a concurrent indolent lymphoma and those with the GCB subtype had a higher rate of late relapse, owing to increased relapses with indolent lymphoma. Patients who relapsed with DLBCL had a worse prognosis than those who relapsed with indolent lymphoma.

Indolent B-cell lymphomas other than follicular lymphoma account for up to 10% of all B-cell neoplasms. While they typically follow a slowly progressive course, some patients experience rapid progression and early mortality. Prognostic scoring systems have not been adopted, hindering the ability of clinicians or researchers to predict outcomes, or risk-stratify patients during clinical trials. To address this, we evaluated the utility of existing prognostic indices and novel, early disease-related outcomes, to predict subsequent long term survival. Baseline characteristics and outcomes data were generated from a longitudinal cohort study that prospectively enrolled 632 patients newly diagnosed with marginal zone lymphoma, lymphoplasmacytic lymphomas, or B-cell lymphomas not otherwise specified, beginning in 2002. The International Prognostic Index (IPI), Follicular Lymphoma International Prognostic Index (FLIPI), and MALT International prognostic index (MALT-IPI) demonstrated c-statistics that ranged from 0.593-0.612 for event-free survival (EFS), and 0.683-0.714 for overall survival (OS). Patients who attained event-free survival at 12 months (EFS12) experienced similar mortality to the US general population (standardized mortality ratio [SMR] 1.19; 95% CI 0.95-1.46). Patients who did not attain EFS12 had subsequent worse morality (SMR 3.14 (95% CI 2.05-4.59). The MALT-IPI demonstrated utility in predicting subsequent long-term outcomes among patients with non-follicular indolent B-cell lymphomas. This index should be used by clinicians giving guidance to patients at the time of initial diagnosis, and risk stratification during clinical studies. The divergent long-term outcomes experienced by patients who do or do not attain EFS12 suggest there exists a subset of patients who harbor high-risk disease. Future research efforts should focus on methods to identify these patients at the time of diagnosis, in order to enable risk-tailored therapy.

Some patients with diffuse large B-cell lymphoma (DLBCL) present with a concurrent indolent lymphoma at diagnosis. Their outcomes in the rituximab era are not fully defined. Using a prospectively followed cohort of 1324 newly diagnosed DLBCL patients treated with immunochemotherapy, we defined the prevalence, characteristics, and outcome of DLBCL with concurrent indolent lymphoma. Compared with patients with DLBCL alone (n = 1153; 87.1%), patients with concurrent DLBCL and follicular lymphoma (FL) (n = 109; 8.2%) had fewer elevations in lactate dehydrogenase, lower International Prognostic Index (IPI), and predominantly germinal center B-cell–like (GCB) subtype, whereas patients with concurrent DLBCL and other indolent lymphomas (n = 62; 4.7%) had more stage III-IV disease and a trend toward higher IPI and non-GCB subtype. After adjusting for IPI, patients with concurrent DLBCL and FL had similar event-free survival (EFS) (hazard ratio [HR] = 0.95) and a trend of better overall survival (OS) (HR = 0.75) compared with patients with DLBCL alone, but nearly identical EFS (HR = 1.00) and OS (HR = 0.84) compared with patients with GCB DLBCL alone. Patients with concurrent DLBCL and other indolent lymphomas had similar EFS (HR = 1.19) and OS (HR = 1.09) compared with patients with DLBCL alone. In conclusion, DLBCL patients with concurrent FL predominantly had the GCB subtype with outcomes similar to that of GCB DLBCL patients. DLBCL patients with concurrent other indolent lymphoma had similar outcomes compared with patients with DLBCL alone. These patients should not be summarily excluded from DLBCL clinical trials.

Purpose Although the life expectancy of patients with follicular lymphoma (FL) has increased, little is known of their causes of death (CODs) in the rituximab era. Patients and Methods We pooled two cohorts of newly diagnosed patients with FL grade 1-3A. Patients were enrolled between 2001 and 2013 in two French referral institutions (N = 734; median follow-up 89 months) and 2002 and 2012 in the University of Iowa and Mayo Clinic Specialized Program of Research Excellence (SPORE; N = 920; median follow-up 84 months). COD was classified as being a result of lymphoma, other malignancy, treatment related, or all other causes. Results Ten-year overall survival was comparable in the French (80%) and US (77%) cohorts. We were able to classify COD in 248 (88%) of 283 decedents. In the overall cohort, lymphoma was the most common COD, with a cumulative incidence of 10.3% at 10 years, followed by treatment-related mortality (3.0%), other malignancy (2.9%), other causes (2.2%), and unknown (3.0%). The 10-year cumulative incidence of death as a result of lymphoma or treatment was higher than death as a result of all other causes for each age group (including patients ≥ 70 years of age at diagnosis [25.4% v 16.6%]) Follicular Lymphoma International Prognostic Index score 3 to 5 (27.4% v 5.2%), but not Follicular Lymphoma International Prognostic Index score 0 to 1 (4.0% v 3.7%); for patients who failed to achieve event-free survival within 24 months from diagnosis (36.1% v 7.0%), but not for patients who achieved event-free survival within 24 months of diagnosis (6.7% v 5.7%); and for patients with a history of transformed FL (45.9% v 4.7%), but not among patients without (8.1% v 6.2%). Overall, 77 of 140 deaths as a result of lymphoma occurred in patients whose FL transformed after diagnosis. Conclusion Despite the improvement in overall survival in patients with FL in the rituximab era, their leading COD remains lymphoma, especially after disease transformation. Treatment-related mortality also represents a concern, which supports the need for less-toxic therapies.

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event-free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1-3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re-treatment, or death due to any cause. OS was compared to age-and-sex-matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR = 3.72, 95%CI: 2.78-4.88; Lyon SMR = 8.74, 95%CI: 5.41-13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR = 0.73, 95%CI: 0.56-0.94, Lyon SMR = 1.02, 95%CI: 0.58-1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR = 17.63, 95%CI:11.97-25.02, Lyon SMR = 19.10, 95%CI:9.86-33.36; EFS24 failure: MER SMR = 13.02, 95%CI:9.31-17.74, Lyon SMR = 7.22, 95%CI:4.13-11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL. Am. J. Hematol. 91:1096-1101, 2016. © 2016 Wiley Periodicals, Inc.

Immune dysfunction is a hallmark of CLL/MBL; ~25% individuals with newly diagnosed CLL have hypogammaglobulinemia at diagnosis. In this study of newly diagnosed CLL/MBL, we sought to a) investigate the association between serum immunoglobulins and specific mutations identified by next generation sequencing, and b) determine if serum immunoglobulin levels predict TFT, independent of the CLL-International Prognostic Index (CLL-IPI) and tumor mutational load (TML). We used the Mayo Clinic CLL Resource to identify newly diagnosed CLL/MBL individuals consented within 2 years of diagnosis. Baseline clinical characteristics and the CLL-IPI score was ascertained on all individuals. DNA was extracted from peripheral blood CD5+/CD19+ clonal B-cells; and the entire coding regions of 60 somatically recurring mutated CLL driver genes were enriched using a customized Agilent SureSelect gene panel and sequenced in Illumina Hiseq4000. Serum immunoglobulins were quantitated by radial immunodiffusion using Immunoplates. The relationship between serum immunoglobulins was assessed: a) with individual gene mutations (mutated vs. not); and b) using the TML score (using a value of 0, 1, and 2 or greater [2+] mutated genes). The impact of serum immunoglobulin levels on TFT was analyzed for all individuals. Of 356 individuals identified, 80 (22%) had MBL, median age was 63 years (28-87), 261 (73%) were male, and the CLL-IPI distribution was: low risk (n=149, 42%), intermediate risk (n=112, 32%), and high/very high risk (n=94, 26%). We observed 43%, 39%, and 18% individuals with 0, 1, or 2+ mutated genes, respectively. The most commonly mutated genes were NOTCH1 (13%), SF3B1 (13%), TP53 (8%), ATM (8%), BIRC3 (7%), and NFKBIE (7%). Using standard cutoffs, 135 (38%) individuals had low serum IgG, 73 (21%) had low serum IgA, and 154 (44%) had low serum IgM at diagnosis. There were no differences in individual gene mutation frequencies between individuals with low and normal serum IgG. In contrast, individuals with low serum IgA were more likely to have mutations in NOTCH1 (25% vs 10%) and ATM (14% vs 7%) compared to those with normal IgA, and individuals with low serum IgM were more likely to have mutations in NOTCH1 (19% vs 9%) and BIRC3 (11% vs 4%) compared to those with normal IgM (all p-values After a median follow-up of 6.9 years, 157 individuals required CLL therapy. After adjusting for CLL-IPI and TML, low serum IgG, low serum IgA, and low serum IgM (hazard ratio [HR]: 1.8, 2.3, and 2.4, respectively, all p-values Our study shows that individuals with CLL/MBL who harbor mutations in NOTCH1, ATM and BIRC3 are more likely to have low serum IgA and IgM at diagnosis. Serum IgA and IgM (but not serum IgG) levels decrease with an increase in the TML score. Finally, low serum immunoglobulins can predict TFT, independent of the CLL-IPI and TML, which has important implications for risk stratification in newly diagnosed CLL/MBL. Citation Format: Sameer A. Parikh, Cristine Allmer, Geffen Kleinstern, Nicholas J. Boddicker, Shulan Tian, Cecilia B. De Campos, Laura A. Bruins, Daniel R. o"brien, Brian F. Kabat, Kari G. Rabe, Aaron D. Norman, Huihuang Yan, Xing Li, Timothy G. Call, Wei Ding, Jose F. Leis, Saad J. Kenderian, Celine M. Vachon, James R. Cerhan, Neil E. Kay, Susan L. Slager, Esteban Braggio. Serum immunoglobulins are an independent prognostic marker of time to first therapy in newly diagnosed chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6466.

Background Factors associated with chronic immune stimulation such as transplantation, autoimmune disorders and chronic infections have been linked to the development of lymphoma, while atopic conditions have been associated with a lower risk of lymphoma. Vaccinations, in part due to their ability to induce immune responses, have been hypothesized to play a role in lymphoma etiology, but there are few studies with mixed results and limited data on lymphoma subtypes. Methods We used a clinic-based study of 2461 newly diagnosed lymphoma cases and 2253 frequency-matched controls enrolled from 2002-2015. Participants self-reported lymphoma risk factors and history of vaccinations for hepatitis A, hepatitis B, chicken pox, yellow fever and influenza. Pathology was centrally reviewed, and included 644 chronic lymphocytic leukemia, 528 follicular (FL), 414 diffuse large B-cell (DLBCL), 170 marginal zone, 127 mantle cell, 119 T-cell, 181 Hodgkin, and 278 other lymphoma subtypes. We used polytomous logistic regression to estimate odds ratio (OR) and 95% confidence intervals (CI) of vaccinations with lymphoma risk overall and for subtypes, adjusting for age, sex, socioeconomic status, body mass, alcohol use, smoking history, recreational sun exposure, and family history of hematological malignancies. Results The median age at diagnosis for lymphoma cases was 64 years (range: 18-93) and 58% were male; the median age at enrollment for controls was 62 years (range: 18-91) and 53% were male. The most common vaccinations among controls were influenza (90%) followed by hepatitis B (41%), hepatitis A (30%), chicken pox (20%), and yellow fever (11%). Vaccination for influenza was inversely associated with lymphoma risk overall (OR=0.75, CI:0.61-0.93, P=0.01), with an inverse trend for increasing number of vaccinations (P=0.0001). In subtype analyses, Influenza vaccination was inversely associated with risk of FL (OR=0.59, CI:0.43-0.80, P=0.001), DLBCL (OR=0.64, CI:0.44-0.92, P=0.02) and other lymphoma subtypes (OR=0.66, CI:0.43-1.00, P=0.05). Vaccination for hepatitis A was inversely associated with lymphoma risk (OR=0.79, CI:0.65-0.96, P=0.02), with no significant subtype-specific associations. No evidence of association with vaccination for hepatitis B (OR=0.95, CI:0.79-1.14) and chicken pox (OR=0.83, CI:0.68-1.02) for lymphoma risk overall or for any subtypes. Although no evidence of an association with vaccination for yellow fever (OR=0.81, CI:0.62-1.06) for lymphoma risk, it was inversely associated with DLBCL risk (OR=0.42, CI:0.22-0.80). Conclusion Vaccination for influenza and hepatitis A were inversely associated with overall lymphoma risk. DLBCL was associated with vaccination for influenza and yellow fever. FL was associated with vaccination for influenza. Understanding the underlying mechanisms for a putative protective effect of certain vaccines could provide new clues to the etiology and prevention of lymphoma. Citation Format: Geffen Kleinstern, Dennis P. Robinson, Carrie A. Thompson, Melissa C. Larson, Cristine Allmer, Grzegorz S. Nowakowski, Timothy G. Call, Stephen M. Ansell, Andrew L. Feldman, Neil E. Kay, Thomas M. Habermann, Susan L. Slager, James R. Cerhan. Vaccination history and risk of lymphoma and its major subtypes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1054.

e19112 Background: We sought to study the longitudinal QOL, financial burden and perception of care (PoC) in patients with multiple myeloma (MM) or lymphoma (LYM) enrolled on CTs vs. those receiving standard care (Non-CT). Methods: QOL was evaluated using the FACT-G questionnaire (baseline, 1, 2, 3, 6 & 12 months). Financial burden was evaluated using 10 questions adapted from the MEPS survey and PoC was evaluated using 6 questions adapted from the CAHPS survey (baseline, 3, 6 & 12 months). Results: 35 (28%) of 123 enrolled patients were treated on CTs. Demographics, QOL and financial burden are shown in the Table. Baseline QOL scores were similar in CT vs non-CT groups. Age, gender and self-reported performance status were significantly associated with baseline QOL, while lines of therapy & cancer type were not. There were no significant differences in change in QOL vs. baseline in patients treated on CTs vs. non-CTs at 1, 2, 3, 6 and 12 months from baseline, including the total FACT-G score and the subdomains of functional, physical, emotional and social well-being. Within each group, there was a decline in QOL over the first 3 months, specifically physical WB, which gradually returned to baseline. Baseline answers to financial burden questions were similar, except patients on CTs reported less need for taking extended time-off from work (22% vs. 46%, p = 0.02). The only statistically significant difference in individual Qs over 1 year was ‘worry about having to pay large medical bills’ at the 6-month timepoint (CT: 0%, non-CT: 52%, p = 0.01). Using a composite score from 4 MEPS questions, financial burden over time was lower in the CT group, though the differences were not statistically significant. There were no significant differences in PoC at baseline, 3, 6 and 12 months in the two groups based on answers to each of the six questions adapted from the CAHPS survey. Conclusions: Over 1 year, patients on CTs experienced a similar QOL and perceived their care to be similar as non-CT patients. Financial burden was lower in the CT group, though differences were not statistically significant. [Table: see text]

The impact of physical activity (PA) on lymphoma survival is not known. The association of PA and change in PA with overall (OS), lymphoma-specific (LSS) and event-free (EFS) survival was evaluated in a prospective cohort of newly diagnosed lymphoma patients (2002-2012). We calculated Leisure Score Indexes (mLSI) from the self-reported usual adult PA (baseline) and at 3-years post-diagnosis (FU3), grouping patients by active vs insufficiently active by the American Cancer Society PA guidelines. Associations of PA with survival were assessed using hazard ratios (HRs) and 95% confidence intervals (CI) from Cox models stratified by lymphoma subtype, adjusted for age, sex, baseline BMI, and comorbidity score with change scores further adjusted for baseline PA. Three thousand sixty participants were evaluable at baseline and 1371 at FU3. Active patients had superior survival from baseline [HR (CI): OS 0.82 (0.72-0.94); LSS 0.74 (0.61-0.90); EFS 0.92 (0.82-1.02)] and FU3 [HR (CI): OS 0.64 (0.46-0.88); LSS 0.32 (0.18-0.59); EFS 0.82 (0.61-1.10)] compared to insufficiently active. An increase in mLSI from baseline to FU3 (vs stable mLSI) was associated with superior OS (HR = 0.70, CI 0.49-1.00) and LSS (HR = 0.49, CI 0.26-0.94).The continuous change in mLSI at FU3 was significantly associated with OS, LSS and EFS; maintained across subgroups and appeared linear. Higher PA among lymphoma patients at diagnosis and 3 years is significantly associated with OS, LSS, and EFS. Increasing PA after diagnosis is significantly associated with improved OS and LSS supporting an important role for PA in lymphoma survivorship and the need for intervention trials.

Background With lymphoma survival rates increasing and a growing population of long-term survivors, the development of cardiovascular disease (CVD) in this patient population is of increasing importance. Anthracyclines are critical in the management of many lymphoma subtypes. However, there is a risk of developing anthracycline-induced CVD. Here, we estimate the cumulative incidence of CVD in adult lymphoma survivors and investigate risk factors associated with post diagnosis CVD. Methods Participants were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). From 2002-2015, the MER offered enrollment to all patients with newly diagnosed lymphoma who are US residents and age >18 years. Participants completed a risk factor questionnaire, and clinical and treatment data were abstracted from medical records. Patients were contacted every 6 months for the first 3 years after diagnosis and annually thereafter to assess disease status, re-treatment and new onset morbidity including CVD. CVD events, including congestive heart failure (CHF), coronary artery disease (CAD), valvular heart disease (VHD), and arrhythmia were identified and validated against medical records. CHF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. CAD, arrhythmia, and VHD were validated using clinical definitions. We calculated the cumulative incidence of CVD, with death modeled as a competing risk. The association of risk factors and treatments with risk of CVD was estimated using hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression with a competing risk of death. Risk factors included age, sex, diabetes, smoking, body mass index (BMI), and treatment with anthracyclines or radiation therapy. Results The study consisted of 3,063 lymphoma patients after excluding those with chronic lymphocytic leukemia and CVD prior to lymphoma diagnosis. The median age at diagnosis was 59 years (range 18-95), and 56% were males. At a median follow-up was 6.9 years (range 0.8-17.1), 640 patients (21%) had died without CVD and 485 patients self-reported CVD post lymphoma diagnosis, of which 280 (57.7%) were validated. Cardiovascular events included 86 CHF, 78 CAD, 40 VHD, and 164 arrhythmias. The cumulative incidence of CVD (Figure 1) at 5 and 10 years was 6.0% (95% 5.2%-7.0%) and 10.7% (95% CI 9.5%-12.1%), respectively. In multivariable analysis, increasing age (HR=3.93 per 5 years, p30 kg/m2 (HR=1.50, p=0.01), and anthracycline treatment (HR=1.49. p6 anthracycline cycles was 5%, 6.9%, 7.4%, and 7.7%, respectively. Adjusting for cardiac risk factors, the number of anthracycline cycles was significantly associated with increased risk of CVD (1-5 cycles HR=1.34, p=0.11; 6 cycles HR=1.51, p6 cycles HR=2.04, p=0.03). Furthermore, the number of anthracycline cycles was associated with CHF (1-5 cycles HR=2.82, p6 cycles HR=5.33, p6 cycles HR=1.65, p=0.27). Conclusions In the modern treatment era, the risk of new onset CVD in patients with lymphoma without a history of CVD is approximately 1% per year after diagnosis. Arrhythmia and CHF were the most commonly occurring CVD events in this cohort. Both traditional CVD risk factors and treatment with anthracyclines was associated with an increased risk of developing CVD, and anthracyclines were a risk factor for arrhythmia and CHF in particular. Prevention of CVD in lymphoma patients will need to address both treatment and traditional lifestyle factors. Figure 1 Disclosures Maurer: Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Celgene: Research Funding. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.

Introduction. The VES-13 is a simple, self-reported, function based tool originally developed to screen community-dwelling populations to identify persons age 65 years and older at risk of death and functional decline, including death in the next 12 months. The VES-13 items include patient's age, self-rated overall health status, functional limitations in physical activity, and functional disabilities in more complex activities of daily living. As part of the Lymphoma Epidemiology of Outcomes (LEO) cohort study, we collected self-reported VES-13 data at study enrollment on all participants regardless of age, and here we report on the prevalence of vulnerable status defined by the VES-13 and its association with 1-year mortality, overall, stratified at age 65 years, and in the subset of diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy. Methods. From 7/2015 to 6/2017, 3253 participants with NHL were enrolled within 6 months of their diagnosis into the LEO cohort. 2004 were evaluable on VES-13, and 1183 (59%) completed it before the initiation of therapy. VES-13 scores range from a minimum of 0 (low risk for decline) to a maximum of 10 (greatest risk for decline), and a score ≥3 was classified as vulnerable. Clinical, pathology and treatment data were abstracted using a standard protocol, and participants were contacted every 6 months for the first three years and then annually thereafter to identify outcomes. Medical records were reviewed by LEO clinicians to classify cause of death according to a standard protocol. Therapy was determined by the treating physician, and this was independent of knowledge of the VES-13 score. The association of VES-13 with 1-year mortality from date of diagnosis was estimated using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models, which also provided model c-statistics. Results. The median age of the 2004 participants in this analysis was 62 years (range 18-94); 57% were male; 54% were ≥65 years; and 28% had a normal body mass index (BMI), 1% were underweight, 35% were overweight, and 36% were obese. Clinically, 59% of participants had an aggressive subtype, 65% were stage III-IV, 24% had B-symptoms, and 11% had a performance status (PS) of ≥2. Overall, 28% of participants were classified as vulnerable (95% CI 26%-30%), with a higher prevalence among those completing the survey after initiation of therapy (38%, 95% 34%-41%) versus before initiation of therapy (22%, 95% CI 20%-24%), and a higher prevalence for those ≥65 years (32%, 95% CI 29%-34%) versus Conclusion. Based on a self-administered VES-13, 28% of newly diagnosed NHL patients in the LEO cohort were classified as vulnerable, including 25% of those Disclosures Martin: Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Casulo:Gilead: Honoraria, Other: Travel, accommodation, expenses; Celgene: Research Funding; Roche: Other: Travel, accommodation, expenses. Cohen:Takeda Pharmaceuticals North America, Inc.: Research Funding; Bristol-Meyers Squibb Company: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; UNUM: Research Funding; Gilead/Kite: Consultancy; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding. Farooq:Kite Pharma: Research Funding; Celgene: Honoraria. Friedberg:Acerta: Other: Data & Safety Monitoring Committee; Bayer: Honoraria, Other: Data & Safety Monitoring Committee. Kahl:Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Consultancy; TG Therapeutics: Consultancy. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Maurer:Nanostring: Research Funding; Celgene: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees. Nastoupil:Spectrum: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding. Rutherford:Heron: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Juno Therapeutics Inc: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Flowers:National Cancer Institute: Research Funding; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; Acerta: Research Funding; TG Therapeutics: Research Funding; Millenium/Takeda: Research Funding; AstraZeneca: Consultancy; Optimum Rx: Consultancy; V Foundation: Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Denovo Biopharma: Consultancy; Gilead: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding.

Purpose The development of cardiovascular disease (CVD) is a relatively rare but a clinically important adverse event in the treatment of lymphoma, particularly in individuals receiving anthracyclines. There are few studies assessing the role of germline genetic susceptibility as a predictor of CVD in this setting. We evaluated the association of 24 single nucleotide polymorphisms (SNPs) from candidate genes involved in anthracycline-induced cardiotoxicity, CVD, and venous thromboembolism with new-onset CVD in a prospective cohort of lymphoma patients treated in the modern era. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE. Enrollment from 2002-2015 was offered to patients with newly diagnosed lymphoma who were age ≥18 years. Clinical, pathology and treatment data were abstracted using a standard protocol, and participants provided a peripheral blood sample, from which DNA was extracted. All patients were prospectively contacted every 6 months for the first 3 years from diagnosis and then annually thereafter to assess disease status, re-treatment and development of new morbidities, including CVD. Reported CVD events included congestive heart failure (CHF), coronary heart disease (CHD), arrhythmia, valvular heart disease (VHD), and other CVD. These events were identified during follow-up and validated against medical records. Genotyping was conducted using a custom Illumina iSelect platform with rigorous quality controls. For each SNP, Cox regression was used to estimate Hazard Ratios (HRs) and 95% confidence intervals (CI) with time to first CVD, using death without CVD as a competing risk. HRs were also obtained for time to CHF, using death without CVD as a competing risk. We also modeled these events for all patients and for patients receiving frontline anthracyclines. Each SNP was modeled as having a log-additive (per minor allele) effect in the regression model. An ordinal test was used to assess the trend, with a nominal P Results There were a total of 3,063 newly diagnosed lymphoma patients (excluding chronic lymphocytic leukemia) with no history of CVD at time of lymphoma diagnosis, of which 1280 had genotype data available for analysis. The median age at diagnosis was 59 years (range, 18-95) and 56% were male. The most common subtypes were follicular (26.3%), diffuse large B-cell (23.2%), Hodgkin (11.3%), marginal zone (11.2%), mantle cell (6.3%) and T-cell (5.4%) lymphoma. Anthracycline-based chemotherapy as initial therapy was used in 52% of individuals. At a median follow-up of 6.9 years (range, 0.1-17.1), 363 (30.7%) patients died, and 173 (13.5%) had new-onset CVD after lymphoma diagnosis. There were 234 incident CVD events in the 173 patients: 49 CHD, 50 CHF, 27 VHD, 103 arrhythmias, and 5 other CVD. Results are shown in the Table. When assessing all CVD, F5 (rs4524) (HR=1.28, 95% CI=1.03-1.58) and F11 (rs4253399) (HR=1.30, 95% CI=1.06-1.61) were associated with CVD at P Conclusions In this exploratory study of candidate SNPs from the literature, we found limited evidence for a role of germline genetic variability in predicting risk of CVD or CHF in a cohort of lymphoma patients, especially after accounting for multiple testing. To fully address this hypothesis, future studies will need larger sample sizes and more comprehensive genetic assessment. Disclosures Maurer: Celgene: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding. Nowakowski:NanoString: Research Funding; Genentech, Inc.: Research Funding; MorphoSys: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Curis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Celgene: Consultancy, Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees. Cerhan:Celgene: Research Funding; NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.

Autoimmune conditions are strong risk factors for developing lymphoma, but their role in lymphoma prognosis is less clear. In a prospective cohort study, we evaluated self-reported history of eight autoimmune conditions with outcomes in 736 diffuse large B-cell, 703 follicular, 302 marginal zone (MZL), 193 mantle cell (MCL), 297 Hodgkin lymphoma (HL), and 186 T-cell lymphomas. We calculated event-free survival (EFS) and overall survival (OS), and estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sex, prognostic score, and treatment. History of any of the eight autoimmune conditions ranged from 7.4% in HL to 18.2% in MZL, and was not associated with EFS or OS for any lymphoma subtype. However, there was a positive association of autoimmune conditions primarily mediated by B-cell responses with inferior EFS in MCL (HR = 2.23, CI: 1.15–4.34) and HL (HR = 2.63, CI: 1.04–6.63), which was largely driven by rheumatoid arthritis. Autoimmune conditions primarily mediated by T-cell responses were not found to be associated with EFS or OS in any lymphoma subtype, although there were few events for this exposure. Our results indicate that distinguishing autoimmune conditions primarily mediated by B-cell/T-cell responses may yield insight regarding the impact of this comorbid disease, affecting ~10% of lymphoma patients, on survival.

We evaluated the association of Human Pegivirus (HPgV) viraemia with risk of developing lymphoma, overall and by major subtypes. Because this virus has also been associated with better prognosis in the setting of co-infection with human immunodeficiency virus, we further assessed the association of HPgV with prognosis. We used risk factor data and banked plasma samples from 2094 lymphoma cases newly diagnosed between 2002 and 2009 and 1572 frequency-matched controls. Plasma samples were tested for HPgV RNA by reverse transcription polymerase chain reaction (RT-PCR), and those with RNA concentrations

Our aim was to evaluate whether quality of life (QOL) scores at diagnosis predict survival among patients with aggressive lymphoma. Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE and systematically followed for event-free and overall survival (OS). QOL was measured with the Functional Assessment of Cancer Treatment-General (FACT-G), which measures 4 domains: physical, social/family, emotional, and functional well-being (WB); a single item Linear Analogue Self-Assessment (LASA) measuring overall QOL; and a spiritual WB LASA. From 9/2002 to 12/2009, 701 patients with aggressive lymphoma who completed baseline QOL questionnaires were enrolled. At a median follow-up of 71 months (range 6-128), 316 patients (45%) had an event and 228 patients (33%) died. All baseline QOL measures but emotional WB were significantly associated with OS (all P 0.04); of which all but LASA spiritual remained significant after adjusting for IPI and NHL subtype. The strongest associations were with total FACT-G (adjusted HR = 0.86, 95% CI: 0.79-0.94, P = 0.00062) and functional WB (adjusted HR = 0.88, 95% CI: 0.83-0.93, P .0001). QOL LASA was associated with OS (adjusted HR = 0.92, 95% CI: 0.87-0.97, P = 0.0041). Patients with clinically deficient QOL (overall QOL ≤50) had a median OS of 92 months compared with 121 months for patients with QOL50 (P = 0.0004). In this large sample of patients with aggressive lymphoma, we found that baseline QOL is independently predictive of OS. QOL should be assessed as a prognostic factor in patients with aggressive lymphoma.

The prevalence, presenting clinical and pathological characteristics, and outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr virus positive remain uncertain as does the impact of congenital or iatrogenic immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma with available tissue arrays were identified from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource. Patients infected with human immunodeficiency virus or who had undergone a prior organ transplant were excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on all tissue arrays. A history of significant congenital or iatrogenic immunosuppression was determined for all patients. At enrollment, 16 of the 362 (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%) patients had a significant history of immunosuppression. Patients with Epstein-Barr-positive diffuse large B-cell lymphoma had no unique clinical characteristics but on pathology exhibited a higher frequency of CD30 positivity (25.0% versus 8.1%, respectively; P

Mantle cell lymphoma (MCL) is a unique type of lymphoma with a prognosis intermediate between indolent and aggressive types. The purpose of this study was to study blood cytokine levels in newly diagnosed and relapsed MCL patients with respect to patterns of abnormalities and relationship to the MCL International Prognostic Index (MIPI) score. We analyzed blood levels of 30 cytokines using a multiplex ELISA in 88 patients with newly diagnosed MCL (pre-treatment levels) and 20 with relapsed MCL and compared them with controls without known lymphoma. Elevated cytokine levels were compared with clinical outcome and the MIPI score. In the 88 newly diagnosed MCL patients, we found significantly elevated levels compared with controls of IL-12, IP-10, sIL-2Rα, MIG, IL-1RA, IL-8, MIP-1α, and MIP-1β (all P

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 × 10−5). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.

There are few studies examining complementary and alternative medicine (CAM) use and beliefs among nonHodgkin lymphoma (NHL) survivors. Seven hundred and nineteen patients with NHL from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. Altogether 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was associated with increased overall CAM use ( p 0.0001) as well as use of vitamins ( p 0.0001), herbals ( p 0.006) and alternative therapy ( p 0.0002) for cancer. Older age ( 60) was associated with increased vitamin use ( p 0.005) and decreased herbal use ( p 0.008). Among users, 143 (20%) believed CAM assists healing, 123 (17%) believed CAM relieves symptoms, 122 (17%) believed CAM gives a feeling of control, 110 (15%) believed CAM assists other treatments, 108 (15%) believed CAM boosts immunity, 26 (4%) believed CAM cures cancer and 36 (5%) believed CAM prevents the spread of cancer.

The detection of serum free light (FLC) is useful in the diagnosis of several hematological diseases. The role and biological relevance of monoclonal or polyclonal FLC elevations in predicting long-term outcome in diffuse large B-cell lymphoma (DLBCL) is unknown. We determined the relationship of the type of FLC elevations to outcome, tumor genotype, and pattern of serum cytokine elevations in 276 patients with untreated DLBCL. Elevated FLC was an adverse prognostic factor through 6 years of follow-up (monoclonal, Event free survival (EFS) HR = 3.56, 95% CI: 1.88–6.76, P

Background: The frequency of preventive health practices (PHP), including age-appropriate screening for malignancies and immunizations, and compliance with PHP guidelines in lymphoma survivors is not known. We hypothesized that lymphoma survivors are more compliant with PHP than the general population but PHP rates may differ based on patient, disease and treatment characteristics. Methods: We identified eligible lymphoma patients from the SPORE Molecular Epidemiology Resource (MER) cohort, in which they were prospectively enrolled within 50 years and compliant if they had fecal occult blood test Results: Of 4248 lymphoma patients enrolled in the MER from 2002 to 2012, 2038 participants completed FU3. 1105 (54%) were male. The median age at diagnosis was 61 (IQR 51-69) years. There were equal numbers of indolent (N=1002) and aggressive (N=995) histologies with follicular (N=515, 25%) and diffuse large B-cell (N=427, 21%) being the most common. Majority (N=1221, 60%) had advanced stage (Ann Arbor III-IV) disease. 469 (23%) had events prior to FU3 and majority 1777 (88%) had received lymphoma treatment prior to FU3. Of 2038 survivors who completed FU3, 1576 (79%) reported having colon cancer screening in their lifetime. 1328 (91%) of 1570 eligible survivors were compliant, 124 (9%) were not and 118 had missing information. Survivors of age >60 years (93% vs 88%, p 872 (96%) of 933 female survivors reported having a breast exam and 836 (91%) had a mammogram at least once in their lifetime. 495 (96%) of 561 eligible female survivors were compliant, 23 (4%) were not and 43 had missing information. There was no difference in mammographic screening based on age (60), histology (indolent vs aggressive), events prior to FU3, treatment prior to FU3 or year of diagnosis (2010-2012 vs 2002-2009). 737 (78%) of 1105 male survivors had a PSA test at least once in their lifetime. 115 (71%) of 216 eligible men were compliant, 47 (29%) were not and 54 had missing information. There was no difference in PSA screening by age (60), histology (indolent vs aggressive), events prior to FU3, and treatment prior to FU3. 1818/2038 (90%) survivors had received an influenza vaccine in their lifetime. 1567 (81%) were compliant, 373 (19%) were not and 98 had missing information. Survivors >60 years of age (87% vs 75%, p As a comparison in the US general population [Figure], between 2002-2015 the highest rates published by the Center for Disease Control are 62% for colon cancer screening (2015), 75% for mammography (insured, 2003) and influenza vaccination 42% (2015). Per the American Cancer Society, the highest rate of PSA screening was 54% (2010). Conclusion: Lymphoma survivors have high compliance with PHP recommendations compared to the general population. Although older individuals and those with indolent histologies were more likely to receive influenza vaccination and colon cancer screening, this difference was not seen in breast and prostate cancer screening practices. Lymphoma treatment and events did not seem to affect the frequency of PHP among survivors. Figure. Figure. Disclosures Cerhan: Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding.

Introduction: The addition of Rituximab to chemotherapy has significantly improved the outcome of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients treated with immunochemotherapy for DLBCL who achieve EFS24 (event-free for 2 years after diagnosis) have an overall survival equivalent to that of the age- and sex-matched general population. Relapses after achieving EFS24 have been considered to be unusual but have been understudied. We sought to define the rate, clinical characteristics, treatment pattern, and outcomes of such relapses. Methods: 1448 patients with newly diagnosed DLBCL from March 2002 to June 2015 were included. Patients were enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, treated per physician choice (predominantly R-CHOP immunochemotherapy) and followed prospectively. An event was defined as progression or relapse, unplanned re-treatment after initial therapy, or death from any cause. Cumulative incidence of relapse and non-relapse mortality after achieving EFS24 were analyzed as competing events using Gray's test in the EZR software. Post-relapse survival was defined as time from relapse to death from any cause and analyzed using Kaplan-Meier method in SPSS (V22). Results: Among the 1448 patients, 1260 (87%) had DLBCL alone at diagnosis, and 188 (13%) had concurrent indolent lymphoma (follicular lymphoma 115, marginal zone lymphoma 18, chronic lymphocytic leukemia 14, lymphoplasmacytic lymphoma 4, unspecified 37) at diagnosis. After a median follow-up of 83.9 months, 896 patients achieved EFS24. For all 896 patients who achieved EFS24, the cumulative incidence of relapse (CIR) was 5.7%, 9.3% and 13.2%, respectively, at 2, 5 and 10 years after achieving EFS24. Patients with concurrent indolent lymphoma at diagnosis had a higher CIR compared to those with DLBCL alone at diagnosis (10.2 vs 4.8% at 2 years, 15.7 vs 8.0% at 5 years, 28.8 vs 9.7% at 10 years, P There were a total of 84 patients who relapsed after achieving EFS24. The median age at initial diagnosis was 66 years (range 35-92), and 48 (57%) were male. At diagnosis, 11 (13%) had ECOG PS >1, 37 (50%) had LDH elevation, 62 (74%) were stage III-IV, 14 (17%) had more than 1 extranodal site, and 26 (31%) were poor risk by R-IPI score. There were 58 patients with DLBCL alone at diagnosis who relapsed after achieving EFS24, and 38 (75%) relapsed with DLBCL, 13 (25%) relapsed with indolent lymphoma (predominantly follicular lymphoma), and pathology was unknown in 7 patients. In contrast, there were 26 patients with concurrent indolent lymphoma at diagnosis who relapsed after achieving EFS24, and 9 (41%) relapsed with DLBCL, 13 (59%) relapsed with indolent lymphoma, and pathology was unknown in 4 patients. In the 47 patients who relapsed with DLBCL after achieving EFS24, 45% received intensive salvage chemotherapy, 19% received regular intensity chemotherapy, 9% received CNS directed chemotherapy, and 36% went on to receive autologous stem cell transplant (ASCT). In the 26 patients who relapsed with indolent lymphoma after achieving EFS24, 27% were initially observed, 54% received regular intensity chemotherapy, 4% received intensive salvage chemotherapy, and 19% received ASCT after subsequent progression. The median post-relapse survival (PRS) for all patients with a relapse after achieving EFS24 was 38.0 months (95% CI 27.5-48.5). The median PRS for patients who relapsed with DLBCL and indolent lymphoma after achieving EFS24 were 29.9 (19.9-39.9) and 89.9 (NR-NR) months, respectively (P=0.002; Figure 2). Conclusions: Relapses after achieving EFS24 in patients with DLBCL were uncommon in the rituximab era. Patient with DLBCL alone at diagnosis can relapse with either DLBCL or indolent lymphoma (3:1 ratio). Patients with concurrent DLBCL and indolent lymphoma at diagnosis had a significantly higher CIR, and relapses with DLBCL and indolent lymphoma were similar (2:3 ratio). Even with high intensity salvage chemotherapy and consolidative ASCT, patients who relapsed with DLBCL had a significantly worse survival compared to those who relapsed with indolent lymphoma. Late relapses with DLBCL remain clinically challenging, with a median survival of 2.5 years after relapse. Figure 1. Figure 1. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Takeda: Research Funding; Pfizer: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Merck & Co: Research Funding; Bristol-Myers Squibb: Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

Background: Lymphoma survivors are at risk for long term and late effects which may negatively impact quality of life (QOL). Few studies have assessed the impact of change in health behaviors (physical activity (PA), alcohol and smoking) on QOL, specifically in lymphoma survivors. Methods: Patients were prospectively enrolled Results: At baseline, 2805 participants were evaluable for QOL of which 2025 were evaluable at FU3. The median age at diagnosis was 62 (IQR 52-69) years. Majority were males (N=1148, 56.8%), with advanced stage III-IV disease (N=941, 62%) and ECOG performance status At baseline, smoking status was current (N=237), former (N=802), never (N=1310) or not available (NA, N= 456). Current smokers had a significantly lower median QOL scores compared to former and never smokers for EWB (75 vs 79 vs 79, p At baseline, alcohol use status was current (N=1189), former (N=506), never (N=518) and NA (N=592). Current alcohol users had the highest FWB (79 vs 75 vs 75, p At baseline, participants with PA in the high vs low LSI tertile had significantly better median scores for FWB (79 vs 75, p=0.01), SFWB (93 vs 89, p In a sensitivity analysis, QOL was modeled for health behaviors in the subset of patients with QOL assessed prior to treatment; results were consistent with the QOL in all patients. Conclusions: Health behaviors in lymphoma survivors are significantly associated with QOL: better QOL is associated with not smoking, more PA, and moderate alcohol use. Current alcohol consumption, as opposed to former alcohol use, may be related to overall health status. An increase in PA after lymphoma diagnosis is associated with an increase in the QOL. Thus, modification of health behaviors has the potential to impact QOL in lymphoma survivors. Figure. Figure. Disclosures Cerhan: Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

Backgroud. The treatment landscape of mantle cell lymphoma (MCL) has significantly changed in last decades. Improvement in diagnosis and understanding of disease biology has been coupled with emergence of new therapeutic options, including targeted agents. While MCL outcome data comes primarily from clinical trials (CT), the impact of therapeutic advances on pattern of care (POC) and outcome in MCL in the general population is not well characterized. This study sought to characterize changes in pattern of care and outcomes of patients with MCL in a prospective observational series in the rituximab era. Methods. The study included consenting adult patients with newly diagnosed MCL that were prospectively enrolled into the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource, from 09/01/2002 to 06/30/2015. Demographic, clinical and prognostic factors were abstracted, and all patients were actively followed for re-treatment, relapse and death. Since bendamustine-rituximab (BR) regimen starting to be used in 2010, we defined patients enrolled from 09/01/2002 to 12/31/2009 as era 1 and those enrolled 01/01/2010 to 06/30/2015 as era 2. Baseline characteristics and outcomes, evaluated in terms of event free survival (EFS), overall survival (OS) and cause of death, were analyzed and compared between the two eras identified. Results. 348 patients with newly diagnosed MCL were enrolled. Five patients had no available data for front-line treatment and were excluded. The analysis was thus conducted on 343 patients: 169 patients were diagnosed in era 1 with a median follow-up of 131.2 months vs. 174 in era 2 with a median follow-up of 58.9 months. Baseline clinical characteristics and MIPI score were similar across the two eras ( Table 1). Frontline induction treatment was significantly different in the two eras. BR use was 0 vs 49 (28.2% ), R-CHOP/CHOP like regimen in 89 (52.7%) vs 45 (25.9%), high-dose cytarabine (HiDAC)-based therapy in 1 (0.6%) vs 28 (16.1%), intensified regimens (HyperCVAD) in 16 (9.5%) vs 8 (4.5%), other regimens (including R-cladribine, R-fludarabine-mitoxantrone, rituximab monotherapy) in 35 (20.7%) vs 13 (7.5%) patients in era 1 vs era 2 respectively. Non-systemic treatment (observation, surgery or radiation only) was performed in 25 (14.8%) vs 31 (17.8%), while 9 (8%) vs 12 (7.7%) patients were enrolled in clinical trials, in era 1 vs era 2 respectively. Autologous stem cell transplantation (ASCT) as consolidation of first line treatment or use of Rituximab maintenance was not different between Era 1 and Era 2. Among the entire cohort of 343 MCL patients, 3y-EFS and 3y-OS were 51.9% (95% IC 46.7-57.6) and 73.5 (95% CI 68.8-78.4), respectively (Figure 1). 3y-EFS was 45.9% (95% CI 39.0-54.1%) vs 58.4 (95% CI, 51.2-66.6%) in Era 1 vs Era 2 (HR 0.69 (0.51-0.92), p=0.006), 3y-OS was 70.9% (95% CI, 63.4-78.1%) vs 76.1% (95% CI, 69.7-83.1%) in Era 1 vs Era 2 (HR 0.87 (0.61-1.24), p=0.26), respectively (Figure 1). In a univariate analysis, high risk simplified MIPI was prognostic of lower EFS and OS in both the era groups. Conclusion. The BR regimen entered front line therapy of MCL resulting in decline of R-CHOP use in the MER. While rates of ASCT remain similar over the two eras, high dose cytarabine usage in induction therapy has increased. While POC in MCL continue to evolve, the introduction of bendamustine and high-dose citarabine based regimens resulted in an improvement in EFS but not OS in this observational cohort-based analysis. Findings in this study are important for design and planning of future clinical trials incorporating novel agents in induction therapy of MCL. Figure 1. Figure 1. Disclosures Cohen: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

Introduction Primary testicular lymphoma (PTL) and testicular involvement of systemic lymphoma (secondary testicular lymphoma, STL) are uncommon. Most testicular lymphomas are aggressive B-cell lymphomas and portend a high risk of extranodal relapse, including CNS relapse. As such, when testicular lymphoma is identified, the management strategy is often changed to include CNS prophylaxis. It is, therefore, essential to evaluate testicular involvement in diagnosis and staging. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a standard imaging modality to stage aggressive lymphoma. Physiologic testicular FDG activity can be challenging to distinguish from involvement by lymphoma given a wide range of normal. An imaging threshold for testicular PET uptake would be clinically relevant and would help guide management. We compare testicular FDG avidity in testicular lymphoma with physiologic testicular FDG avidity. Methods Records of patients (pts) diagnosed with PTL or STL from 2002-2018 enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource were reviewed, yielding 36 pts with testicular lymphoma. Physiologic testicular avidity by FDG PET/CT was determined from analysis of 70 randomly selected patients who received FDG PET/CT from 2013-2018 prior to treatment for non-lymphoma indications including pulmonary nodule, lung carcinoma, head & neck squamous cell carcinoma, gastrointestinal carcinomas, and metastatic melanoma, without known hematologic malignancy, testicular pathology, or history of testicular infection/surgery by medical chart review. Imaging parameters compared in this analysis were SUVmax and SUVmean. All FDG PET/CT exams were reviewed centrally by a nuclear medicine radiologist and a radiology resident. Results Of the 36 pts with testicular lymphoma, 19 had an orchiectomy prior to FDG PET/CT and 7 pts did not have a staging FDG PET/CT scan. Of the 10 pts with intact testes at the time of staging FDG PET/CT, 1 pt with low-grade lymphoma was excluded. 9 pts with aggressive lymphomas were included in this analysis: 7 pts with diffuse large B cell lymphoma (DLBCL), and 1 pt each with Burkitt lymphoma and peripheral T-cell lymphoma, not otherwise specified. Testicular lymphoma was diagnosed by orchiectomy in 3 pts, and by percutaneous biopsy in 3 pts. 3 pts did not have tissue sampling of testes or scrotal contents, but had an overtly FDG-avid testicle highly suggestive of lymphomatous involvement. These 3 pts had biopsy-proven lymphoma in parotid, bone marrow, and stomach, respectively, with mean testicular SUVmax 6.8 among the 3 pts. The median age in this analysis cohort was 62 years (range 35-88). Of the 7 analyzed DLBCL pts, 6 were non-germinal center B-cell, and 1 was germinal center B-cell. The 70 control pts had a median age of 55 years (range 18-90). In known testicular lymphoma cases and control pts, SUVmax and SUVmean were assessed from the most FDG-avid testicle. Median SUVmax for the testicular lymphoma cases was 13.3 (range 5.5-29.9), compared to a median of 3.8 (range 2.1-5.5) for controls (Wilcoxon p Conclusions FDG PET/CT shows significantly greater FDG avidity for testicular aggressive lymphomas as compared with physiologic testicular FDG uptake in this single institution study with centralized radiology review of cases and controls. Testicular FDG avidity greater than an SUVmax 5.0 in staging aggressive lymphoma is highly suggestive for testicular involvement, warranting follow-up clinical exam and ultrasound, at a minimum. In addition, testicles with SUVmax Figure. Figure. Disclosures Witzig: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

Background: To address the current and long-term unmet health needs of the growing population of patients diagnosed with non-Hodgkin lymphoma (NHL) and NHL survivors, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/) with recruitment at eight centers (Cornell University, Emory University, Mayo Clinic, MD Anderson, University of Iowa, University of Miami, University of Rochester, and Washington University). Here we report on the first two years of enrollment. Methods: All patients ≥18 years with NHL (exclusive of chronic lymphocytic leukemia) newly diagnosed within 183 days of enrollment are eligible. LEO reviews all pathology diagnoses; annotates and harmonizes all cases with clinical, epidemiologic, pathology and treatment data; builds a NHL tumor bank that includes an H&E slide, a formalin-fixed, paraffin-embedded tissue sample and extracted tumor DNA and RNA; collects peripheral blood and banks DNA, serum, plasma and buffy coat in a central biorepository; and prospectively follows patients regularly to ascertain disease progression/relapse, retreatment, transformation, second cancers, survival, updated exposures, and patient-reported outcomes. We examined the demographics, clinical characteristics, and NHL subtypes for patients enrolled in the first two years (2015-2017) in LEO Cohort and compared these characteristics to population-based registry data from the United States Surveillance, Epidemiology, and End Results (SEER) Program for 2011-2015. We also examined baseline body mass index (BMI), comorbidities and quality of life (QOL) measured with the Functional Assessment of Cancer Therapy - General (FACT-G) scores (0-100 scale) overall and by NHL subtype that were collected in LEO but not available in SEER or any other large, prospective US NHL cohort. Results: From 2015-2017, LEO enrolled 3244 NHL patients across 47 states (Figure) with a median age at diagnosis of 62 years (range, 18-94 years) and 55.9% male. Based on self-identified race/ethnicity, 85% of the participants were White, 7.4% were Black/African American, 2.6% were Asian, and 3.5% other or more than one race; 9.9% were Hispanic (regardless of race). The most common subtypes were diffuse large B-cell (DLBCL, 33.9%), follicular (FL, 22.2%), mantle cell (MCL, 9.3%), marginal zone (MZL, 8.3%), T-cell (TCL, 10.9%), and all other NHL subtypes (other NHL, 15.3%). These distributions were all within 5% of SEER data, except that 6.8% of participant in LEO were in the age 80+ years group compared to 18.5% in SEER (Table). The overall prevalence of self-reported comorbidities at enrollment was 13.5% for heart disease (range, 12.1% for FL to 16.6% for MCL), 8.8% for diabetes (range, 7.1% for FL to 9.8% for DLBCL), 4.6% for osteoporosis (range, 3.0% for MCL to 6.3% for MZL), and 5.9% for autoimmune disease (range, 2.0% for MCL to 12.6% for MZL). The median BMI was 27.9 kg/m2 (range, 26.7 kg/m2 for TCL to 28.3 kg/m2 for MZL). A total of 2151 participants completed the FACT-G with a median score of 78.7 (range, 75.9 for TCL to 83.3 for MZL). Complete IPI data were available on 2296 participants: 40.4% IPI 0-1, 32.7% IPI 2, 18.3% IPI 3, 8.7% IPI 4-5. Overall, 73.7% of participants were initially treated with systemic therapy (range, 40.0% for MZL and 91.8% for DLBCL); 14.5% were initially managed with observation (range, 1.4% DLBCL and 31.8% for FL); and 2.0% were initially manage with radiotherapy (range, 0.2% for MCL and 3.8% for DLBCL). Outcomes are being prospectively collected. Conclusions: LEO is a large and diverse cohort of newly diagnosed NHL patients and the first two years of enrollment reflects the broader United States NHL population. Enrollment is ongoing. This unique resource will enable examination of the interactions among a broad array of clinical and molecular factors and their impact on multiple outcomes, to improve prognostication, identify new approaches to improve outcomes and survivorship, and facilitate clinical trials using this infrastructure. Disclosures Flowers: Acerta: Research Funding; Pharmacyclics/ Janssen: Consultancy; OptumRx: Consultancy; Janssen Pharmaceutical: Research Funding; V Foundation: Research Funding; Burroughs Wellcome Fund: Research Funding; Spectrum: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Abbvie: Consultancy, Research Funding; Bayer: Consultancy; Millennium/Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Gilead: Consultancy; BeiGene: Research Funding; Karyopharm: Consultancy; Denovo Biopharma: Consultancy; Genentech/Roche: Consultancy; Gilead: Research Funding; Genentech/Roche: Research Funding; National Cancer Institute: Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding. Nastoupil:TG Therappeutics: Research Funding; Merck: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Research Funding; Spectrum: Honoraria; Gilead: Honoraria; Genentech: Honoraria, Research Funding; Karus: Research Funding; Novartis: Honoraria; Juno: Honoraria. Kahl:Acerta: Consultancy; Genentech: Consultancy; Seattle Genetics: Consultancy; Juno: Consultancy; CTI: Consultancy; ADC Therapeutics: Consultancy; Gilead: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy. Casulo:Celgene: Research Funding; Gilead: Honoraria. Friedberg:Bayer: Honoraria. Lossos:Affimed: Research Funding. Martin:Seattle Genetics: Consultancy; Kite: Consultancy; Janssen: Consultancy; Gilead: Consultancy; Bayer: Consultancy; AstraZeneca: Consultancy. Leonard:Bayer: Consultancy; Celgene: Consultancy; Biotest: Consultancy; United Therapeutics: Consultancy; BMS: Consultancy; MEI Pharma: Consultancy; Juno: Consultancy; Sutro: Consultancy; Karyopharm: Consultancy; ADC Therapeutics: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Genentech/Roche: Consultancy; Novartis: Consultancy. Bernal-Mizrachi:Kodikaz Therapeutic Solutions: Consultancy, Equity Ownership; Takeda Pharmaceutical Company: Research Funding. Maurer:Morphosys: Research Funding; Nanostring: Research Funding; Celgene: Research Funding. Cerhan:Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding.

IF 5.67; International audience

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P, Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPP associated with risk of this disease.

Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.