MYD88^L265P and MYD88^other variants show different molecular characteristics and prognostic significance in diffuse...

This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88^L265P and MYD88^other.

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.

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).

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.