Patients with mantle cell lymphoma (MCL) and central nervous system (CNS) involvement at relapse who were treated with ibrutinib had longer overall survival (OS) than patients treated with blood-brain barrier (BBB)-crossing chemotherapy or other treatments, according to the results of a multicenter, retrospective study published in the journal Blood.

MCL relapse with CNS involvement is rare and has no standard treatment. Ibrutinib can cross the BBB, and thus was hypothesized to potentially improve outcomes compared with other treatment approaches.

This multicenter, retrospective, observational study evaluated data from 88 patients with MCL and CNS disease at relapse who received CNS-directed treatment between 2000 and 2019. There were 3 cohorts, including patients treated with ibrutinib, those treated with high-dose methotrexate with or without cytarabine, and other treatments. The primary endpoint was OS.

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The median age of all cohorts was 63 years, and 76% of patients were men. A quarter of patients had an ECOG performance status of 2 to 4, and 89% of patients had extranodal involvement. The median number of treatment lines prior to CNS relapse was 1 (range, 1-5), and the median time from MCL diagnosis to relapse was 16 months (range, 1-122).

The objective response rate (ORR) was 78% with ibrutinib, which was significantly higher than the 46% for BBB-crossing chemotherapy (P =.031) The ORR was 33% for other types of treatment.

At a median follow-up of 29.5 months, ibrutinib was associated with improved OS and progression-free survival (PFS). The median OS was 16.8 months with ibrutinib and 4.4 months with chemotherapy (P =.007). The median PFS was 13.1 months with ibrutinib and 3.0 months with chemotherapy (P =.009). The OS and PFS of patients treated with other therapies was not reported.

In a multivariate analysis, ibrutinib was independently associated with a significant improvement in OS (hazard ratio [HR], 6.8; 95% CI, 2.2-21.3; P<.001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P =.002). CNS disease progression within 24 months of MCL diagnosis was significantly associated with shorter OS (HR, 2.4; 95% CI, 1.1-5.3; P =.026) and PFS (HR, 2.3; 95% CI, 1.1-4.6; P =.023). The addition of intrathecal chemotherapy was not associated with improved OS (P =.502).

“Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered a therapeutic option,” the study authors concluded.

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.


Rusconi C, Cheah CY, Eyre TA, et al. Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse. Blood. 2022;140:1907-1916. doi: 10.1182/blood.2022015560