A French Multicentric Prospective Cohort of 6000 Patients with Integrative Epidemiological, Clinical, Biological and Treatment Data to Improve Knowledge on Outcome of Lymphoma Patients: Pilot Phase Results of the Real World Data in Lymphoma and Survival in Adults (REALYSA) Study

Introduction: Lymphoma incidence continues to rise in France since early 80', although differently among subtypes. Recent improvements in patient survival in major lymphoma subtypes at populational level raise new questions about patient outcome (in specific subgroups) and survivorship (i.e. quality of life, long term sequelae). Numerous epidemiological studies have investigated factors related to lymphoma risk, but far fewer have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour achieved from clinical trials data is partly biased because of patient selection.

Study Design and Methods: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set in France areas mostly covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow up. ClinicalTrials.gov identifier is NCT03869619. We aim to include 6000 patients over 4 years. Adult patients without lymphoma history and newly diagnosed of one of the following 7 lymphoma subtypes (diffuse large B cell (DLBCL), follicular (FL), marginal zone (MZL), mantle cell (MCL), Burkitt, Hodgkin (HL), T-cell (T-NHL)) are offered to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. After having given signed informed consent, participants fill in three auto-questionnaires regarding lifelong history of residences and occupations, quality of life (QoL / QLQ-C30 questionnaire) and social support (SS / SSQ6 questionnaire). Patients are then interviewed to collect their sociodemographic characteristics, medical and familial history, professional and domestic exposures to major chemicals and pesticides, lifestyle and women health. Clinical data are obtained using patients medical records, including care pathway, medical history, concomitant treatments, initial diagnosis characteristics, nodal/extra-nodal involvement, exams performed, staging, laboratory data, serologic tests, geriatric screening (G8 questionnaire), treatments received (including pre-phase, detailed treatment phases and molecules, reasons for treatment discontinuation), progressions, and treatment response evaluation. Biological samples at baseline and during treatment are collected including plasma and peripheral mononuclear cells. Additionally, a virtual tumor biobank is constituted for baseline tumor samples. The diagnosis will be ensured thanks to the review of French Lymphopath network. Follow-up, including clinical outcomes, new morbidities, lifestyle, professional situation, QoL, SS, fertility, health behavior, are collected every 6 months in the first 3 years and every year thereafter.

Results: A pilot phase was implemented between November 2018 and June 2019 in 7 French hospitals/clinics. By June 30, 328 patients were recruited. Biological samples at baseline were obtained for 81% of included patients (n=265). 52% were male and 48% were female. The median age was 62 years (range: 18-95). The histological subtypes were the following (n=308 patients with complete data): 132 DLBCL (42.8%); 59 FL (19.5%); 52 HL (16.9%); 29 MCL (9.4%); 22 MZL (7.1%); 13 T-NHL (4.2%); 1 other (0.3%). We observed a good adherence to clinical research process despite the complexity of data collection. An extension phase with 10 additional centres will be launched during the last 2019 trimester.

Discussion: The pilot phase of REALYSA study showed a good compliance to study guidelines and a good quality of data collected at baseline. Consequently, the study design is prospectively feasible in real-life setting. This cohort will constitute an innovative platform for clinical, biological, epidemiological and socio-economical research projects.