Treatment of bing neel syndrome: Using a sledgehammer to crack a nut?

Introduction: Bing Neel syndrome (BNS) is a rare complication of Waldenström's Macroglobulinaemia (WM) comprising direct infiltration of the CNS by lymphoplasmacytic lymphoma. Asymptomatic patients need active surveillance; symptomatic patients require treatment. Systemic and intrathecal chemo/immune therapy and BTK inhibitors are effective, but their optimum deployment remains unclear. Methods: Data from 30 WM and 2 MZL patients with CNS involvement were extracted from the Rory Morrison Registry for WM; 5 with DLCBL histology were excluded. Diagnostic data are presented separately. Responses are reported as per Minnema et al. (2017). Results: 27 patients with BNS were evaluated (16 female, 11 male). Median age at WM/MZL diagnosis was 62 (36-71) and BNS diagnosis was 68 (53-74). A median of 1 prior line of therapy was given for WM (range 0-7). First line therapies for BNS: MATRix in 14 (54%) [4 cycles in 6, 3 cycles in 1, 2 cycles in 6 and 1 ongoing]; IDARAM in 6 (23%) [4 cycles in 2; 2 and 3 cycles in one each and 1 cycle in 2]; HD MTX +/-R +/-ARA-C was given in 3 (12%); IT MTX following systemic chemo in 1 (4%); Ibrutinib 1 (4%) and Fludarabine-R 1 (4%). The majority (74%) showed a partial response, with CR in 4 (15%). In 9 (45%) patients, treatment was consolidated for different reasons (to limit toxicity, to deepen response): Rituximab in 3 (30%); Ibrutinib in 3 (30%); ASCT in 2 (20%); IT MTX in 2 (20%) and IT Rituximab in 1 (10%). Three patients (12%) had no response and 2 (8%) progressed through first line therapy; 2 (8%) patients are inassessible due to ongoing therapy. Relapse occurred in 5 patients at a median time of 17 months (3-81); 4 (80%) patients received second line therapy all achieving a response (including 1 CR). Median overall survival from BNS diagnosis was not reached; 7/27 (30%) of patients have died; 3/7 (43%) from disease progression, 1/7 (14%) from sepsis during treatment, 1/7 (14%) treatment-unrelated, 1/7 (14%) unknown (likely disease progression). Of the 7 who died; median age at death 69 (55-74); median survival from diagnosis of WM/MZL 122 months (6-232); median survival from BNS diagnosis 3 months (0-13). Conclusions: Our results suggest that the use of adapted intensive regimens +/-consolidation with Rituximab or BTK Inhibitor induces a prolonged remission with limited toxicity. Further investigation including a prospective multicentred clinical trial is required to help elucidate optimum treatment in BNS.