An integrated prognostic model for diffuse large B-cell lymphoma treated with immunochemotherapy

Diffuse large B-cell lymphoma (DLBCL), the most frequent non-Hodgkin's lymphoma subtype, is characterized by strong biological, morphological, and clinical heterogeneity, but patients are treated with immunochemotherapy in a relatively homogeneous way. Here, we have used a customized NanoString platform to analyze a series of 197 homogeneously treated DLBCL cases. The platform includes the most relevant genes or signatures known to be useful for predicting response to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) in DLBCL cases. We generated a risk score that combines the International Prognostic Index with cell of origin and double expression of MYC/BCL2, and stratified the series into three groups, yielding hazard ratios from 0.15 to 5.49 for overall survival, and from 0.17 to 5.04 for progression-free survival. Group differences were highly significant (p < 0.0001), and the scoring system was applicable to younger patients (<60 years of age) and patients with advanced or localized stages of the disease. Results were validated in an independent dataset from 166 DLBCL patients treated in two distinct clinical trials. This risk score combines clinical and biological data in a model that can be used to integrate biological variables into the prognostic models for DLBCL cases.Funding information: GILEAD, Grant/Award Numbers: PIE15/0081, PI16/01294, PI17/2172, PI17/00272, PI19/00715, GL18/00019; Asociación Española Contra el Cáncer, Grant/Award Number: PROYE18054PIRI; Instituto de Salud Carlos III, Grant/Award Number: PT17/0015/0024; Xarxa de Bancs de Tumors de Catalunya; Biobank do Complexo Hospitalario Universitario de Santiago de Compostela, Grant/Award Number: PT17/0015/0002; Hospital Universitario Virgen del Rocío-Instituto de Biomedicina de Sevilla Biobank, Grant/Award Number: PT17/0015/0041; Valdecilla Biobank, Grant/Award Number: PT17/0015/0019;MD Anderson Biobank, Grant/Award Number: PT17/0015/0008; AIRC (Italian Association for Cancer Research, Milan, Italy), Grant/Award Number: 5×1000 n. 21198; Marie Skłodowska-Curie Individual Fellowship, Grant/Award Number: 882597; CIBERONC, Grant/Award Number: CB16/12/00291; Comunidad Autonoma de MadridDLBCLGene expressionImmunochemotherapyDiffuse large B-cell lymphomaPrognosi

An integrated prognostic model for diffuse large B‐cell lymphoma treated with immunochemotherapy

Abstract Diffuse large B‐cell lymphoma (DLBCL), the most frequent non‐Hodgkin's lymphoma subtype, is characterized by strong biological, morphological, and clinical heterogeneity, but patients are treated with immunochemotherapy in a relatively homogeneous way. Here, we have used a customized NanoString platform to analyze a series of 197 homogeneously treated DLBCL cases. The platform includes the most relevant genes or signatures known to be useful for predicting response to R‐CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) in DLBCL cases. We generated a risk score that combines the International Prognostic Index with cell of origin and double expression of MYC/BCL2, and stratified the series into three groups, yielding hazard ratios from 0.15 to 5.49 for overall survival, and from 0.17 to 5.04 for progression‐free survival. Group differences were highly significant (p < 0.0001), and the scoring system was applicable to younger patients (<60 years of age) and patients with advanced or localized stages of the disease. Results were validated in an independent dataset from 166 DLBCL patients treated in two distinct clinical trials. This risk score combines clinical and biological data in a model that can be used to integrate biological variables into the prognostic models for DLBCL cases