A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy

Abstract

Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

“…33, 34 This study, enrolling the largest number of de novo DLBCL patients with positive BM involvement to date, allowed valuable and effective analysis and confirmed that there is heterogeneity in the positive BM cohort.…”

Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B‐cell lymphoma

“…3 Conversely, as the most common extranodal site, GI tract involvement indicated favorable prognosis, which remains controversial among previous studies. 3,28,29 As for genetic alterations, we provided genomic evidence corresponding to clinical data in extranodal DLBCL. Oncogenic mutations were frequently observed in patients with lymphoma invasion of the bones, kidney/adrenal glands (MYD88), 30 spleen (BCL6, IRF8, KMT2D, and SOCS1), [31][32][33][34] lungs (FAS and NFKBIE), 35,36 and liver (BCL6), 31 but less often in patients with GI invasion (MYD88, PIM1, MEPG1, DUSP2, and HIST1H1E).…”

Monoclonal gammopathies regardless of subtypes are associated with poor prognosis of diffuse large B-cell lymphoma

“…[ 3 ] However, the International Prognostic Index (IPI), which was developed in the era of chemotherapy treatment for aggressive lymphoma, has proven to be less powerful in the rituximab era. To better distinguish tumor prognosis, several models [ 4 , 5 ] and algorithms [ 6 , 7 ] have been developed. In addition, several markers have been discovered in DLBCL, to better identify patients who will likely have a poor therapeutic response.…”