Efficacy and Safety of an Orelabrutinib-Based Oral Induction Regimen in Central Nervous System Lymphoma: A Real-World Study.

PURPOSE: To evaluate the efficacy and safety of an orelabrutinib-based RBTL regimen (rituximab, orelabrutinib, temozolomide, and pomalidomide) as an induction strategy for patients with central nervous system lymphoma (CNSL).

PATIENTS AND

METHODS

We retrospectively analyzed 40 patients with CNSL treated at the Affiliated Hospital of Qingdao University between April 2022 and January 2025, including 28 newly diagnosed and 12 relapsed/refractory patients. RBTL was administered as induction therapy, followed by individualized subsequent treatment, including high-dose methotrexate (HD-MTX)-based therapy, radiotherapy, autologous stem cell transplantation, or maintenance therapy. The primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, and safety.

RESULTS

Forty patients were evaluable for safety and 38 for efficacy. All 38 efficacy-evaluable patients received subsequent individualized therapy after RBTL induction, including HD-MTX-based therapy, radiotherapy, ASCT, or orelabrutinib maintenance. After RBTL induction, the ORR was 86.8% (33/38), including a complete response/unconfirmed complete response (CR/CRu) rate of 36.8%. After subsequent therapy, the best ORR was 94.7% (36/38), with a CR/CRu rate of 63.2%. With a median follow-up of 18.5 months, the 12-month PFS and OS rates were 74.7% (95% CI, 61.6-90.6%) and 71.3% (95% CI, 57.7-88.2%), respectively. Treatment-emergent adverse events occurred in 92.5% of patients, and 7.5% discontinued treatment because of adverse events. One treatment-related death occurred in association with severe thrombocytopenia.

CONCLUSION

RBTL showed encouraging activity and manageable toxicity as an induction strategy for CNSL. Because most evaluable patients received subsequent individualized therapy, durable disease control should be interpreted in the context of the overall sequential treatment strategy. Larger prospective studies are warranted.