MYD88 L265P Mutation Is a Possible Unfavorable Prognostic Factor in Patients with Diffuse B-Cell Lymphoma

INTRODUCTION

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Activated B-cell like (ABC) molecular subtype DLBCL is characterized by more aggressive behavior and poor clinical outcomes with standard R-CHOP chemotherapy. Approximately 30% of all patients (pts) with ABC DLBCL have recurrent mutation in the MYD88 gene (a change from leucine to proline at position 256 - L256P). We report the impact of the MYD88 mutation status on the clinical course and outcome of pts with ABC DLBCL.

METHODS

In present study MYD88 mutation status was investigated in untreated pts with ABC DLBCL.

The diagnosis of ABC DLBCL was established according to the WHO 2008 classification. DNA from 41 cryopreserved and 12 formalin-fixed paraffin-embedded tumor samples were tested in our study. Sanger sequencing and real-time allele-specific PCR was used to assess MYD88 L265P mutation status.

RESULTS

We report data for 53 pts (34 male, 19 female) with a median age of 53 (18-74) years. MYD88 L265P mutation was detected in 26,4% (14/53) of pts. The international prognostic index (IPI) score was 4-5 in 7/14 (50%) of pts with MYD88 mutated DLBCL and 12/39 (30,8%) pts with MYD88 wild type DLBCL, whereas nearly half of all pts presented with Ann Arbor stage IV disease. The majority of pts 13/14 (93%) with MYD88-positive DLBCL had elevated lactate dehydrogenase levels versus 26/39 (66%) pts with MYD88 unmutated DLBCL. Extranodal was more common in pts with MYD88 mutation than in pts with MYD88 unmutated DLBCL (78,5% vs 54%). All pts received high-dose chemotherapy and were followed for 50,5 (11-95) month. Pts with MYD88 mutation had similar complete response rate comparing to pts without MYD88 mutation (78,6% vs 84,6%). The disease relapsed in 45,4% of pts with MYD88 mutation and in 24,2% of pts without MYD88 mutation. Mortality was in 45,4% of pts with MYD88 mutation and in 24,2% of pts without MYD88 mutation. Overall survival (OS) was better in pts with MYD88 unmutated DLBCL than in pts with MYD88 positive DLBCL (5-year OS, 73% vs 31%).

CONCLUSION

IPI high risk and extranodal involvement is common in ABC DLBCL pts with MYD88 L265P mutation. MYD88 L265P mutation can be a predisposing factor for poor OS probability in pts with ABC DLBCL.