Central Nervous System Involvement in Mantle Cell Lymphoma: Clinical Features, Prognostic Factors and Outcomes from Multi-Centers in China

Background: Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, with the incidence of 3 to 5%. The median survival time was 3 to 6 months. Meanwhile, it is lower in Asia and previously mainly reported by case.

Patients and methods: We present the data on 16 patients with MCL who developed CNS involvement, from a database of 861 consecutively treated patients at 19 institutions.

Results: The crude incidence of CNS involvement in our cohort was 1.9%. In terms of clinical features, 25.0% patients were blastiod MCL, and 50% were high-risk group by MIPI score.46.7% were complex karyotypes. Eleven patients underwent second-generation sequencing, and the results showed the presence of high-risk gene mutations such as TP53 (3/11) NOTCH1 (3/11), ATM (3/11), KMT2D (2/11), CCND1 (2/11). One patient also had CDKN2A deletion and C-myc amplification. 43.8% of patients received high-dose cytarabine treatment, 50.0% received BTKi treatment, and 43.8% received BTKi+BCL-2i. The median treatment lines were 3 (1-6) lines. 75.0% of patients were early disease progression (POD24). The median time from diagnosis to central involvement is 22.0 (4-144) months. Six patients were treated with R-High-dose MTX , six cases were treated with R-BTKi ± other targeted drugs and three patients were treated with R-BTKi -high-dose MTX regimen, and one patient received local radiotherapy. CR and ORR were 12.5% and 31.3%, the median progression free survival after CNS involvement(PFS2) was 2.0 months and the median survival (OS2) was 7.0 months. Elevated levels of β 2-microglobulin, previous used BTKi, and SD/PD were poor prognostic factors for PFS2. In addition to the above factors, ECOG score ≥ 2 were inferior prognostic factors for OS2.

Conclusions: CNS involvement ,especially for patients who involved after BTKi treatment, the prognosis was extremely poor and there was a lack of effective treatment options.

No relevant conflicts of interest to declare.