MYD88 L265P and MYD88 other variants show different molecular characteristics and prognostic significance in diffuse large B-cell lymphoma

Purpose This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88 L265P and MYD88 other . Methods DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88 L265P and MYD88 other were investigated. Results A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88 L265P , while 54 were MYD88 other . MYD88 L265P was more common in non-GCB subtype than MYD88 other (83% vs. 60%, P = 0.004). Besides, MYD88 L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P < 0.001), PIM1 mutation (71% vs. 39%, P < 0.001), and PIM1 hypermutation (28% vs. 11%, P = 0.018), compared with MYD88 other . Compared with MYD88 L265P , MYD88 other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88 other were significantly associated with worse progression free survival (PFS) than those with MYD88 L265P when treated initially with R-CHOP/R-CHOP-like regimen ( P = 0.010). Conclusion The findings of this study indicate that DLBCL patients with MYD88 L265P and MYD88 other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88 other is not superior than those with MYD88 L265P , even poorer when focusing on the non-GCB subtype.