Zanubrutinib plus cytarabine in patients with refractory/relapsed primary central nervous system lymphoma

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare subtype of aggressive extranodal non-Hodgkin lymphoma. Currently, there is no standard of care for the treatment of refractory or relapsed PCNSL (r/r PCNSL). We conducted a prospective single-arm phase II study to evaluate zanubrutinib plus cytarabine for r/r PCNSL. Methods: Using Simon’s two-stage design, we analyzed 34 patients who received high-dose cytarabine (3.0 g/m2 once daily) for 2 days and zanubrutinib (160 mg twice daily) for 21 days each cycle for up to 6 cycles. The study was registered at www.chictr.org.cn as #ChiCTR2000039229. Results: The median follow-up was 19 months. The overall response rate was 64.7% (95% confidence interval CI, 47.9–78.5%) with a complete remission or unconfirmed complete remission rate of 47.1% (16/34) and a partial remission rate of 17.6% (6/34). The median progression-free survival was 4.5 months (95% CI, 1.5–9.4), and the median OS was 18 months (95% CI, 9.5 to not estimable). The median duration of the response was 9 months (95% CI, 3.2 to not estimable). The most common treatment-emergent adverse events were thrombocytopenia (55.9%). No treatment-related death occurred. Conclusion: Zanubrutinib and cytarabine showed efficacy in r/r PCNSL with an acceptable safety profile.