Cns prophylaxis in patients with dlbcl: a real world experience on behalf of the lymphoma subcommittee of the argentine society of hematology

Introduction: Although central nervous system (CNS) relapse in patients with Diffuse Large B-Cell Lymphoma (DLBCL) is an infrequent event, the mortality rate is high. The efficacy of strategies currently used to prevent it, has been challenged. We aimed to evaluate the incidence of CNS relapse, overall survival (OS) and progression-free survival (PFS) in an Argentinian cohort of patients that received CNS prophylaxis as part of their front line treatment. Methods and statistical analysis: Retrospective multicenter national analysis, including patients diagnosed with DLBCL, high grade B-cell lymphoma NOS, double/triple hit, who received CNS prophylaxis from January 2016 to December 2020. We used a Fine and Grey regression model to estimate time to CNS relapse and Kaplan Meier curves for PFS and OS. Results: Two hundred sixty-two patients were included with a median age of 63 years (IQR 53–71), 141 (54%) were male, 222 (85%) had extranodal involvement and 190 (72%) had stage IV at diagnosis. Most frequent extranodal sites were bone (n = 52, 20%), gastrointestinal tract (n = 42, 16%) and bone marrow (n = 37, 14%). IPI was high or intermediate/high in 157 cases (60%), while CNS IPI was intermediate and high in 122 (47%) and 83 (32%), respectively. All patients received immunochemotherapy at diagnosis: 192 (73%) R-CHOP, 62 (24%) R-DA-EPOCH, 8 (3%) others. Two hundred and seven (79%) patients achieved complete response, 18 (6.9%) partial response, 7 (2.7%) stable disease and 30 (11.4%) were primary refractory. Two hundred and seven (79%) patients received intrathecal therapy (ITT), 34 (13%) high doses of methotrexate (HDMTX) and 21 (8%) both. Median ITT was 4 (IQR 3–6). Intercalated HDMTX was administered to 28 (52%) patients, while 26 (48%) received HDMTX at the end of treatment. Forty-one (16%) patients developed toxicity, causing cycling-delays or prophylaxis withdrawal in 20 (8%), respectively. Twenty patients (7.7%) had CNS relapse with an incidence of 2.8% (95% CI 1.4–5.6), 5.8% (95% CI 3.4–9.5) and 7.7% (95% CI 4.9–11.9) at 6, 12 and 24 months, respectively: all of them died of disease progression. We found differences at 24 months between CNS-IPI: 4%, 6.5% and 12% for low, intermediate and high score (p = 0.05). No difference according to type of prophylaxis was found. PFS and OS for the full cohort at 6, 12 and 24 months was 85% (95% CI 80–88), 74% (95% CI 68–79), 62% (95% CI 56–68) and 94% (95% CI 90–96), 83% (95% CI 78–87), 67% (95% CI 61–73), respectively. No statistically significant differences were found in OS and PFS according to type of prophylaxis, no significant risk factors for CNS relapse were found in the bivariate analysis. Keyword: aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.