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Discovery and Validation of a Simplified Scoring System (the PRIMA-Prognostic Index) in De Novo Follicular Lymphoma Treated Initially with Immunochemotherapy

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Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort of patients treated only with initial immunochemotherapy. Given the emergence of new biomolecular and metabolic… Click to show full abstract

Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort of patients treated only with initial immunochemotherapy. Given the emergence of new biomolecular and metabolic prognostic factors in FL, an easy-to-compute and reliable scoring system utilizing such variables could aid in trial stratification and routine clinical evaluation. Methods. The primary endpoint for model building was progression-free survival (PFS). For discovery, we used the large prospective PRIMA trial cohort of 1,135 patients treated with initial R-chemotherapy +/- R-maintenance. Variables considered for model building included age, sex, performance status, B symptoms, stage, number of nodal and extranodal sites involved, LDH, hemoglobin, longest diameter of the largest lymph node, presence of effusion and compression syndrome, circulating lymphoma cells, platelet count, serum albumin, bone marrow involvement, and s2m. For validation, we combined 175 patients with high tumor burden FL from the R-CHVP+interferon arm of treatment from the FL2000 trial and 304 patients prospectively enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) who were treated upfront with immunochemotherapy. Event-free survival (EFS) was the endpoint available in the validation cohort. For model building, we used a two-step approach based on resample Cox regression and conditional inference trees analyses to identify 3 patient groups of approximately equal size and experiencing differential outcome in terms of PFS. For comparison with the FLIPI, model9s discrimination was computed using theConcordance Probability Estimates (CPE) based upon Harrell9s c-index. All statistical tests were 2-sided. A P value Results. The final simplified score based on the discovery set was called the PRIMA-PI (PRIMA-prognostic index) and comprised 3 risk categories: high (s2m > 3 mg/L), low (s2m ≤ 3 mg/L without bone marrow involvement) and intermediate (≤ 3 mg/L with bone marrow involvement). In the discovery cohort, the PRIMA-PI was highly discriminatory with 5-year PFS of 69% (95%CI: 64-73%), 55% (49-60%) and 37% (32-42%) in the low-, intermediate- and high-risk groups respectively (P In the validation cohort, the PRIMA-PI remained highly discriminatory: 5-year EFS was 77% (69-83%), 57% (48-66%) and 44% (35-52%) in the low-, intermediate- and high-risk groups respectively (P Conclusion. We developed and validated a new prognostic tool comprising only 2 parameters (bone marrow involvement and s2m) which are easily measured clinically. The PRIMA-PI is a new and easy-to-compute prognostic index for patients treated upfront with immunochemotherapy. This could serve as a basis for building more sophisticated and integrated biomolecular scores. Disclosures Bachy: Amgen: Honoraria; Sandoz: Consultancy, Honoraria; Mundipharma: Research Funding; Roche/Genentech: Consultancy, Honoraria, Research Funding. Estell: Janssen: Membership on an entity9s Board of Directors or advisory committees. Delmer: Abbvie: Consultancy, Honoraria; Janssen: Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Belada: Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Ansell: Celldex: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Research Funding; Affimed: Research Funding. Lamy: Roche: Consultancy, Honoraria. Cerhan: Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering . Salles: Gilead: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Servier: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Morphosys: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees.

Keywords: entity9s board; honoraria; consultancy honoraria; membership entity9s

Journal Title: Blood
Year Published: 2017

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