Ibrutinib Improves Response and Survival Rates in CNS Relapse of Mantle Cell Lymphoma

Compared with standard immunochemotherapy, treatment with ibrutinib was associated with higher response rates and survival rates in patients with mantle cell lymphoma (MCL) and central nervous system (CNS) relapse, according to the results of a retrospective study presented at EHA25 Virtual, the 25th European Hematology Association Annual Congress.

“CNS relapse in MCL is a rare phenomenon for which a standard of care has not been identified,” said study presenter Chiara Rusconi, MD, of IRCCS National Cancer Institute in Milan, Italy. “Responses to conventional treatment are poor, with fewer than one-third of patients alive at 1 year.”

Ibrutinib has been shown to be effective as a single agent in relapsed or refractory MCL, and case reports and small series have demonstrated its efficacy in CNS disease because of its ability to cross the blood-brain barrier (BBB), Dr. Rusconi explained. In this study, investigators retrospectively reviewed data from 84 consecutive patients with MCL with CNS relapse to evaluate response and survival outcomes among patients who received ibrutinib or standard immunochemotherapy.

Patients presented with CNS relapse between 2000 and 2019. Fifty-eight patients (69%) had been treated with standard immunochemotherapy and 26 (31%) were treated with ibrutinib. Baseline characteristics were similar between the two cohorts, the authors noted. Median ages were 62 and 63 years in the standard and ibrutinib groups, respectively, and the median number of prior therapies was one.

Among those treated with immunochemotherapy, the most commonly prescribed treatments were: rituximab plus BBB-crossing therapy such as high-dose methotrexate (48%), rituximab plus bendamustine-based therapy (11%), intrathecal chemotherapy (29%), and radiotherapy (12%).

Response data were available for 89% of patients. In the immunochemotherapy group, the overall response rate (ORR) was 40%, with a complete response (CR) rate of 17%. In the ibrutinib group, however, the 77% of patients responded to treatment, and 42% achieved a CR.

When the authors looked only at those patients treated with standard therapy including BBB-crossing treatments, the ORR was 46% and the CR rate was 22%. The CR rate was better for those treated with ibrutinib compared with immunochemotherapy with BBB therapy (42% vs. 22%, respectively; p=0.02).

During a median follow-up of 4.3 months, the 1-year overall survival (OS) rate for the entire study cohort was 27%. As with response rates, ibrutinib was associated with a significantly improved 1-year OS rate, compared with immunochemotherapy (61% vs. 16%; p<0.001). In the subgroup of 28 patients who received a BBB-crossing therapy, the 1-year OS rate was 25% – still significantly inferior to patients treated with ibrutinib (p=0.011).

The 1-year progression-free survival rate for the entire cohort was 24%: 58% for the ibrutinib group versus 10% for standard therapy (p=0.003). No major bleeding events or fungal infections were reported.

“With the usual limitations of a retrospective analysis, ibrutinib was associated with improved response and survival compared with standard therapy with more than half of patients still alive at 1 year,” Dr. Rusconi concluded.

Study authors report no relevant conflicts of interest.


Rusconi C, Cheah CY, Tucker D, et al. Ibrutinib compared to immune-chemotherapy
for central nervous system relapse of mantle cell lymphoma: a report from Fondazione Italiana Linfomi (FIL) and European Mantle Cell Lymphoma Network (EMCLN). Abstract S229. Presented as part of EHA25 Virtual, June 12, 2020.