Orelabrutinib combined with rituximab and high-dose methotrexate as induction therapy in newly diagnosed primary central nervous system lymphoma.

OBJECTIVE

Limited treatment options for primary central nervous system lymphoma (PCNSL) highlight the need for alternative therapies. This study evaluated orelabrutinib (O) and rituximab (R), plus high-dose methotrexate (M) (ORM), as a potential induction therapy for newly diagnosed PCNSL.

METHODS

Patients received six cycles of 150 mg/day orelabrutinib, 375 mg/m rituximab, plus 3.5 g/m methotrexate every 3 weeks, followed by autologous hematopoietic stem cell transplantation and orelabrutinib maintenance. The primary endpoint was the overall response rate (ORR) at the end of induction therapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

RESULTS

From October 21, 2020, to October 22, 2024, 28 patients were treated and evaluated for efficacy and safety analyses. At the end of induction therapy, the ORR was 71.4% (95% CI, 51.3-86.8), including 16 (57.1%) complete and 4 (14.3%) partial responses. At a median follow-up of 21.6 months, the median PFS was 35.3 months (95% CI, 8.4-not evaluable), and the median OS was not reached, with PFS and OS rates of 64.3% and 96.3% at 1 year, 64.3% and 90.9% at 2 years, and 45.9% and 82.7% at 3 years, respectively. All 28 (100%) patients experienced treatment-related adverse events (TRAEs) of any grade. Grade 3 TRAEs occurred in seven (25.0%) patients, including five (17.9%) leukopenia, one (3.6%) thrombocytopenia, and one (3.6%) diarrhea. No other Bruton's tyrosine kinase inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) or TRAE-related deaths were observed.

CONCLUSION

The ORM induction regimen showed anti-tumor activity with a favorable safety profile, offering a potential therapeutic strategy for newly diagnosed PCNSL.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov: NCT05600660.