Clinical Features And Prognosis Of 141 Cases Of Treatment-naive Central Nervous System Lymphoma

Background and Purpose:Central nervous system lymphoma（CNSL）is divided into primary central nervous system lymphoma（PCNSL）and secondary central nervous system lymphoma（SCNSL）.The most common pathological type of PCNSL is diffuse large B-cell lymphoma （DLBCL）,accounting for over 90%.Treatment strategies for CNSL include local treatments with surgical resection and whole brain radiation therapy（WBRT）,high dose methotrexate（HD-MTX）based systemic chemotherapy,and small molecule kinase inhibitors.A number of prospective clinical studies have shown that new targeted agents such as bruton’s tyrosine kinase inhibitor（BTKi）and immunomodulatory drugs（IMi Ds）are highly effective and have a good safety profile.They are expected to become first-line treatment options.This study retrospectively analyzed the clinical characteristics,treatment efficacy and prognosis of patients with treatment-naive CNSL and pathological type of DLBCL from the Department of Hematology of the First Hospital of Jilin University.Materials and Methods:1.Retrospective analysis of clinical data of CNSL initially treated at the Department of Hematology of the First Hospital of Jilin University from March 2009 to August 2022,including general features,pathological features,imaging features,treatment efficacy and prognostic features.2.SPSS Statistics 26.0 software was applied for statistical analysis.The measurement data was tested for normal distribution using the Shapiro-Wilk（S-W）method,and those conforming to a normal distribution were described as mean±standard deviation,and differences in means between groups were compared using the independent samples t-test;the count data was expressed as frequencies（%）,and comparisons between groups were made using the chi-square test or Fisher’s exact probability method test.Graph Pad Prism 8was applied to plot survival curves,and log-rank test was applied to compare survival difference between groups.Risk factors were identified using the COX proportional risk model,and factors with P<0.05 in the univariate analysis were included in the multi-factor COX regression analysis.P<0.05 was considered statistically significant（two-tailed）.Results:1.Clinical features of CNSL（1）General information&clinical presentations:A total of 141 treatment-naive CNSL,accounting for 5.6%of lymphomas.CNSL included 116 PCNSL（82.3%）and 25 SCNSL（17.7%）.The median age was 58 years and ratio of men to women was 1.07:1.Median time between onset and presentation was 15 days.The clinical presentations were varied,with symptoms of focal neurological deficits predominating（55.0%）and only 18 cases（12.8%）with B symptoms.The KPS score<70 was found in 61 cases（43.3%）.（2）Pathological examinations:The non-GCB subtype was predominant（89 cases,63.1%）,high Ki-67 expression（≥80%,97 cases,69.8%）;61.7%patients were double-expressed,with no double-hit.Next generation sequencing（NGS）testing,MCD subtype(MYD88^L265P and CD79B co-mutation)was found in 17 cases（56.7%）.Of these,seven cases were treated with BTKi first-line maintenance therapy and five achieved sustained remission.（3）Radiographic examinations:Brain parenchyma was involved in 136 cases（96.5%）,with a predominance of deep（58.7%）and multiple（57.4%）lesions.（4）Prognostic stratification:71.6%of 116 cases of PCNSL were in the high-risk group of MSKCC;76.0%of 25 cases of SCNSL were in the high-risk group of IPI.2.Analysis of survival in different treatment eras of CNSL141 cases of treatment-naive CNSL were divided into three treatment eras,20 cases in2009-2014,30 cases in 2015-2018（initiation of rituximab）and 91 cases in 2019-2022（initiation of new targeted drugs）.Compared to patients in 2009-2014,patients in 2015-2018 and 2019-2022 showed better survival trends.In 2019-2022,patients had a better prognosis,including median progression free survival（PFS）and overall survival（OS）were22 months and 37 months.In 2009-2014,patients had a worse prognosis,including median PFS and OS were 4 months and 15 months.The differences between the two groups were statistically significant（PFS:P<0.001;OS:P=0.010）.3.Subgroup analysis of PCNSL93 patients with PCNSL who underwent surgical resection and completed≥2 courses of HD-MTX induction therapy were included,with a median follow-up time of 36 months,median PFS of 21 months and median OS of 35 months.HD-MTX+rituximab induction therapy significantly improves prognosis in patients with PCNSL.Sequential consolidation or maintenance therapy after induction therapy significantly prolonged PFS and OS.However,there was no significant difference between IMi Ds and BTKi.Haematological toxicity in the IMi Ds group should be given high priority.4.Prognostic analysis of PCNSLAge≥65 years,courses of induction therapy<4 and no maintenance therapy are independent risk factors for PFS in patients with PCNSL.Age≥65 years and no maintenance treatment are independent risk factors for OS.Overall,the important factors associated with prognosis are age and maintenance treatment.Conclusions:1.CNSL is common in the middle-aged and elderly people,with rapid onset and non-specific clinical presentation;pathology is predominantly non-GCB subtype with high Ki-67 expression;imaging mainly involves deep brain parenchyma and multiple intracranial lesions;2/3 of patients are in the medium to high-risk group,with a poor overall prognosis.2.NGS testing revealed 56.7%of patients were classified as the MCD subtype,which responded well to BTKi and can be the main basis for clinical treatment selection.3.The evolution of treatment and outcomes for CNSL patients over time shows that targeted and neo-targeted drugs significantly improve the prognosis of CNSL.4.Sequential consolidation or maintenance therapy after induction therapy significantly improves the prognosis of PCNSL patients,including PFS and OS.5.Significant adverse prognostic factors were age≥65 years,and absence of maintenance treatment.