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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.

AbstractThe 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.

AbstractOur 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 QOL >50 (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.

95 Background: While PA is known to improve quality of life in lymphoma pts, its impact on OS is not known. We studied the effect of PA on OS in lymphoma pts enrolled at diagnosis in the Iowa/Mayo Molecular Epidemiology Resource. Methods: Godin Leisure Score Index (LSI; Range 0-50) was calculated based on level of PA pre-diagnosis (baseline) and 3 years post diagnosis (FU3), with pts grouped by tertile into high, moderate, or low PA. At FU3, pts also reported perceived change in PA since diagnosis. OS was measured as time from assessment (baseline or FU3) until death from any cause. Associations between LSI tertiles and OS were assessed using Cox models adjusted for lymphoma subtype, age and sex. Results: PA level was available for 3060 pts at baseline and 1371 pts at FU3. 95% had an ECOG performance status < 2, 37% had an aggressive subtype, 29% had BMI ≥ 30, and 54% were age > 60. Indolent lymphoma pts with higher PA at baseline had no difference in OS. Higher PA at FU3 had improved OS (moderate vs low HR 0.63, CI 0.42-0.93; high vs low HR 0.53, CI 0.33-0.86). Pts with BMI < 30 who had higher PA at baseline showed no difference in OS. Higher PA at FU3 had improved OS for pts with BMI < 30 (moderate vs low HR 0.68 CI, 0.48-0.98; high vs low HR = 0.41, CI 0.26-0.64). For pts > 60 years, high vs low baseline PA showed improved OS (HR 0.77, CI 0.63-0.93). Higher PA at FU3 (moderate vs low HR 0.68 CI 0.48-0.96, high vs low HR 0.53 CI 0.34-0.83) was associated with OS. At FU3, compared to no change, perceived reduction of PA was associated with worse OS for indolent lymphoma (HR 2.13, CI 1.56-2.91), BMI < 30 (HR 1.95, CI 1.45-2.62), BMI > 30 (HR 2.00, CI 1.21-3.30), age ≤ 60 (HR 3.06, CI 1.72-5.46), and age > 60 (HR 1.98, CI 1.52-2.58). Perceived increase in PA was not associated with OS. Higher PA in pts with aggressive lymphoma, BMI ≥30, and age < 60 was not significantly associated with OS but trended similarly. All results were similar when analyzing by continuous LSI score. Conclusions: Higher levels of PA, especially at FU3, were associated with superior OS. The effect was more pronounced in pts with indolent lymphoma, BMI < 30, or age > 60. Perceived reduction in PA was associated with worse outcomes. PA should be incorporated into lymphoma survivorship plans.

SummaryWe 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 <5000 genome equivalents/ml were confirmed using nested RT‐PCR methods. To assess the role of HPgV in lymphoma prognosis, we used 2948 cases from a cohort study of newly diagnosed lymphoma patients (included all cases from the case‐control study). There was a positive association of HPgV viraemia with risk of lymphoma overall (Odds ratio = 2·14; 95% confidence interval [CI] 1·63–2·80; P < 0·0001), and for all major subtypes except Hodgkin lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma, and this was not confounded by other lymphoma risk factors. In contrast, there was no association of HPgV viraemia with event‐free survival (Hazard ratio [HR] = 1·00; 95% CI 0·85–1·18) or overall survival (HR = 0·97; 95% CI 0·79–1·20) for lymphoma overall, or any of the subtypes. These data support the hypothesis for a role of HPgV in the aetiology of multiple lymphoma subtypes.

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.