Orelabrutinib versus ibrutinib for patients with refractory/relapsed primary central nervous system lymphoma: An efficacy and safety analysis.

Ibrutinib is reported effective in the management of refractory/relapsed primary central nervous system lymphoma but it has adverse effects. Orelabrutinib has received its first approval for the treatment of refractory/relapsed lymphoma either alone or with chemotherapy in China. The objectives of the retrospective study were to evaluate the efficacy and safety of treatment a combination of orelabrutinib (150 mg/day) and rituximab (250 mg/m 2 per week), versus orelabrutinib alone (100 mg twice a day) and ibrutinib alone (560 mg/day) among patients with refractory/relapsed primary central nervous system lymphoma. Patients received 150 mg/day orelabrutinib with 250 mg/m 2 rituximab/week (RO cohort, n = 105) or 100 mg twice in a day orelabrutinib (OB cohort, n = 107) or 560 mg/day ibrutinib (IB cohort, n = 117) until intolerable toxicity. Patients of the OB cohort continue treatment(s) for longer time than those patients of the RO and the IB cohorts ( P < .05 for both). Overall response rate (complete response + partial response) and disease control rates (complete response + partial response + no signs of progressive response) were higher for patients of the RO cohort than those of the IB cohort ( P < .0001 for both). The disease control rate was higher for patients of the OB cohort than those of the IB cohort ( P = .0062). The overall response rate was higher for patients of the RO cohort than those of the OB cohort ( P = .0188). Progression-free survival (from the initiation of disease treatment(s) to disease progression) of patients of the RO and OB cohorts were higher than those of the IB cohort ( P < .0001 for both). Overall survival (from the initiation of disease treatment(s) to death) of the patients of the IB cohort was fewer than those of the RO ( P = .0444) and the OB ( P = .0163) cohorts. Ibrutinib cause bleeding events, and orelabrutinib caused leukopenia, purpura diarrhea, fatigue, and drowsiness. Rituximab and ibrutinib cause fungal infections, atrial fibrillation, bacterial and viral infection(s), hypertension, and tumor lysis syndrome. A total of 150 mg/day oral orelabrutinib plus 250 mg/m 2 intravenous rituximab/week is efficacious and safe for patients with refractory/relapsed primary central nervous system lymphoma (Level of Evidence: IV; Technical Efficacy Stage: 5).