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, according to results of a study published in Blood.

This multicenter, retrospective study included data from 88 patients with MCL and CNS disease at relapse who received CNS-directed treatment between 2000 and 2019. Patients received ibrutinib (n=29), BBB-crossing chemotherapy (high-dose methotrexate with or without cytarabine; n=29), or other treatments (n=30). The primary endpoint was OS.

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).

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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) vs BBB chemotherapy. 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

This article originally appeared on Hematology Advisor