MYD88 L265P mutation in primary central nervous system lymphoma is associated with better survival: A single centre experience

ABSTRACT Background The Myeloid differentiation primary response gene ( MYD88 ) mutation in primary central nervous system lymphomas (PCNSL) may be associated with unfavourable prognosis, however the evidence remains limited. We aimed to comprehensively characterise PCNSLs by integration of clinicopathological, molecular, treatment and survival data. Methods We retrospectively identified and validated 57 consecutive patients with PCNSLs according to the 2017 WHO classification of lymphoid neoplasms over a 13-year period. Formalin-fixed paraffin-embedded tumour samples underwent real-time allele-specific polymerase chain reaction assay to detect MYD88 mutation. We used multivariable Cox regression for survival analysis including age, treatment, and MYD88 as covariates. We searched the literature for studies reporting demographics, treatment, MYD88 and survival of PCNSL patients, and incorporated individual-patient data into our analyses. Results The median age was 66 years and 56% were women. All 57 patients had non-germinal PCNSL and the majority (81%) received either single or combined therapies. There were 46 deaths observed over the median follow-up of 10 months. MYD88 mutation status was available in 41 patients of which 36 (88%) were mutated. There was an association between MYD88 mutation and better survival in the multivariable model (hazard ratio [HR] 0.34; 95% confidence interval [CI] 0.12-0.95; p=0.039) but not in a univariable model. After incorporating additional 18 patients from the literature, this association was reproducible (HR 0.31, 95% CI 0.13-0.77, p=0.012). Conclusions Adjusting for confounders, MYD88 mutation is associated with better survival. While further validation is warranted, identification of MYD88 mutation can identify patients who may benefit from novel targeted therapies. Key points MYD88 mutation is common in PCNSLs. MYD88 mutation in PCNSLs is associated with better survival after adjusting for age at diagnosis and treatment. Identification of MYD88 mutation in PCNSLs can identify patients who may benefit from novel targeted therapies and enhance survival. Importance of the study PCNSLs are rare and associated with lower survival than their systemic counterparts. The emergence of new molecular targets in PCNSLs, such as mutations in the MYD88 gene, offers hope for more effective therapeutics. Few studies have investigated the association between MYD88 mutation and survival. These studies, however, are limited by inconsistent inclusion of clinical variables and suboptimal analytic approach, such as overfitting model or incomplete adjustment for important confounders. Our study integrates treatment, molecular and survival data for 57 patients diagnosed with PCNSL. We demonstrate that without adequate adjustment for confounders such as age at diagnosis and treatment, MYD88 mutation does not affect survival. However, a multivariable survival model including these variables shows MYD88 mutation to be associated with better survival. While further validation of this association is warranted, our findings suggest that identification of MYD88 mutation can identify patients who may benefit from novel targeted therapies and enhance survival.