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

By Olimpia E. Curran, Michael TC Poon, Louise Gilroy, Antonia Torgersen, Colin Smith, Wael Al-Qsous

Posted 09 Sep 2020
medRxiv DOI: 10.1101/2020.09.06.20185827

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 PCNSL of non-germinal centre cell subtype 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.

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