Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era:a report from the International PTL Consortium

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PTDLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P= 0.022) and improved both progression-free survival (PFS, P= 0.012) and overall survival (OS, P= 0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.National Cancer Institute/National Institutes of Health [R01CA138688, 1RC1CA146299, P5OCA136411, P50CA142509]; University of Texas MD Anderson Cancer Center Lymphoma Moonshot Program; Institutional Research and Development Fund; Institutional Research Grant Award; MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award; MD Anderson Cancer Center Myeloma SPORE Research Development Program Award; Gundersen Lutheran Medical Foundation Award; Michael and Susan Dell Foundation; Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center; Roche Molecular System; Gilead Sciences Pharmaceutical; Seattle Genetics; Dai Sanyo Pharmaceutical; Adaptive Biotechnology; HTG Molecular DiagnosticsSCI(E)[email protected]