Ibrutinib-Based Triple Therapy Yields Durable Responses for Newly Diagnosed Primary CNS DLBCL

First-line treatment with ibrutinib, rituximab, and high-dose methotrexate (IRM) produced high and durable response rates with minimal toxicity among patients with newly diagnosed primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL), according to study results published in Frontiers in Oncology.

Previous research has shown promise for the use of Bruton’s tyrosine kinase (BTK) inhibitors, such as ibrutinib, for the treatment PCNS DLBCL. Researchers conducted a single-center pilot study to evaluate the safety and efficacy of ibrutinib, rituximab, and high-dose methotrexate among patients with PCNS DLBCL.

Overall, 9 patients were treated with 4 cycles of ibrutinib, rituximab, and high-dose methotrexate induction, then consolidation therapy by either autologous hematopoietic stem cell transplantation [HSCT] or 2 additional IRM cycles, then followed by ibrutinib/lenalidomide maintenance. Patients were mostly men (n= 7) and the median age to diagnosis was 59 years (range, 48 to 66).

Following induction therapy, the overall response rate (ORR) among treated patients was 100%, including 77.8% with a complete response (CR) and 22.2% with a partial response (PR). Following consolidation, the CR rate rose to 88.9%.

At the median follow-up of 77.6 (range 10.6 to 80.7) months, both 5-year overall survival (OS) and progression-free survival (PFS) were 77.8%. Only 1 patient experienced disease progression and 8 patients remained in sustained CR.

In terms of safety, no treatment-related deaths occurred, and the most common grade ≥3 adverse events were neutropenia and anemia (both 22.2%), and 1 gastrointestinal bleeding event occurred. 

The researchers concluded, our findings suggest that the IRM regimen is a promising first-line therapy for newly diagnosed PCNS DLBCL, particularly for patients ineligible for intensive chemotherapy or ASCT.”

They added, “the combination regimen of high response rates, favorable long-term outcomes, and manageable toxicity underscores its potential clinical utility.”

Source:

Guo Y, Shan Y, Piao Y, et al. Ibrutinib combined with rituximab and high-dose methotrexate in newly diagnosed primary CNS diffuse large B-cell lymphoma: a pilot study with long-term follow-up. Frontiers in Oncology. Published online October 1, 2025. doi:10.3389/fonc.2025.1669385