Clinical Features and Prognosis of Patients with Primary Extranodal Diffuse Large B-Cell Lymphoma

Objective: To investigate the clinical features, gene mutation profile, efficacy and prognostic factors of primary extranodal diffuse large B-cell lymphoma(EN-DLBCL).

Methods: A retrospective analysis was performed for 382 patients with primary EN-DLBCL with complete clinical data who were treated in West China Hospital from January 2013 to January 2023, and their clinical characteristics,gene mutation profile, efficacy and prognostic factors were analyzed.

Results: The median age of the 382 patients with EN-DLBCL was 56(18-89) years old. The male-to-female ratio was 1.12∶1, and the most common primary sites were gastrointestinal tract (31.7%), Wechsler ring (19.1%) and breast gland (7.1%). A total of 51 gene mutations were fund, and the most common frequencies of gene mutations were TP53 (32.5%), MYD88 (32.5%), and CD79B (30.0%). The median follow-up was 63 months, and the 5-year progression-free survival (PFS) rate was 74.5% and the 5-year overall survival (OS) rate was 89.6%. The adverse factors on PFS were as follows: >1 extranodal sites involvement ( P <0.001), P53≥50% ( P <0.001), hyper double expression(hDEL) of C-myc >50%/Bcl-2>70% ( P <0.001). The adverse factors affecting the OS of patients were as follows: >1 extranodal sites involvement ( P <0.001), P53≥50% (P < 0.001), hDEL( P <0.001). Chemotherapy combined with local radiotherapy could improve PFS (P =0.041) and OS (P =0.003), while R-CHOP+X (molecule agents as BTKi、HDACi、Lenalidomide) failed to show a significant difference in PFS (P =0.075) and OS (P =0.767). Among the 40 patients who underwent next-generation sequencing at high risk, there was no significant in PFS (P =0.849) and OS (P =0.500) of patients with positive MYD88 and/or CD79B mutations (MCD subtype) treated with BTKi and patients with negative MYD88 and CD79B mutations.

Conclusions: Primary EN-DLBCL can involve multiple organs or tissue sites. TP53 , MYD88 , and CD79B are the most common gene mutations. The efficacy of BTKi in patients with positive MCD subtypes at intermediate and high risk is not inferior to that in MCD-negative control patients.