Diffuse large b cell lymphoma (DLBCL) presenting with syncrhonous cns and systemic disease at diagnosis: Results from an international collaborative study.

Background: DLBCL presenting with both CNS and systemic disease at first diagnosis is rare. Such patients are excluded from clinical trials; thus, the optimal treatment is unknown and outcomes are poorly described. Aim(s): To describe treatment outcomes of patients with synchronous CNS and systemic DLBCL at first diagnosis. Method(s):Multicentre retrospective international study (6 Australian & UK sites). Cases were identified from clinical and pharmacy records. Eligible patients had histologically proven DLBCL, with radiological, histological, or CSF evidence of synchronous systemic & CNS disease, treated with combination chemotherapy and rituximab. Patients with relapsed disease were excluded. Primary Endpoint: OS. Secondary endpoints: CR rate, PFS, toxicity. P values of <0.05 were considered significant. Result(s): Of 59 patients, 71% were male and the median age was 66yrs (range 17-86). 45 (76%) had NCCN-IPI >=4. Median number of extranodal sites outside the CNS was 2 (range 0-8). 10% were double-hit by FISH, and 35% of those with data available were double-expressors of MYC and BCL2 protein. CNS disease was leptomeningeal only in 24 (41%); 35 (59%) had parenchymal disease, 8 (14%) had both. 34 (58%) received systemic therapy (predominantly R-CHOP, n=31) plus a CNS-directed treatment (group A). 25 (42%) underwent intensified MTX and/or Ara-C containing therapy: hyper-CVAD n=14, CODOX-M/IVAC n=10, DHAC=1 (group B). CNS-directed therapy in group A included: IV HD-MTX in 19 (56%), HDMTX+ Ara-C in 2 (6%), intrathecal therapy (IT) only in 10 (29%), radiotherapy (RT) only in 2 (6%). Specific CNS therapy was omitted in one patient due to early PD. Additional consolidative therapy included CNS RT in 18 (31%) (whole brain in 8, site-specific in 10), and autologous SCT in CR1 in 8 (13%) using BEAM (n=4) or BCNU+thiotepa (n=4) conditioning. All SCT patients were from group B. 23 (39%) required dose reductions and 23 (39%) required early cessation of therapy. Treatment-rela