Investigation of High Dose Cytarabine Plus Zenubrutinib in Relapsed/Refractory Primary Central Nervous System Lymphoma

Background: There is an unmet medical need for the treatment of relapsed/refractory primary central nervous system lymphoma (PCNSL). The first generation of Bruton's kinase (BTK) inhibitor ibrutinib monotherapy has demonstrated efficacy in PCNSL. This study aimed to evaluate the efficacy and toxicity of the second generation of BTK inhibitor zanubrutinib, combined with chemotherapy agent cytarabine in relapsed/refractory PCNSL.

Methods: In this prospective, single-arm, phase 2 trial (ChiCTR2000039229), patients with PCNSL relapsed or refractory to high-dose methotrexate-based treatment were enrolled. High dose cytarabine (3g/m(2) once every day on days 1-2) and zanubrutinib (320mg on days 1-21) was given every 3-week for up to six cycles. Zanubrutinib was held if the platelet count was lower than 50*10⁹/L. Pegylated recombinant human granulocyte stimulating-factor was given at day 3 at each cycle. The primary endpoint was overall response rate (ORR) after chemotherapy.

Results: We enrolled 12 patients with a median age of 59 (range, 26-75) years, of which 6 achieved complete remission and 3 achieved partial remission with an ORR of 75%. Three patients died of tumor progression. With a median follow-up of 12 (range, 1.5-15.5) months, the median progression-free survival was 5.6 months. The median overall survival was not reached. The most common adverse event was thrombocytopenia (75%). Three patients (25%) demonstrated grade 4 thrombocytopenia and all of them recovered soon without platelet transfusion. No drug-related death was reported.

Conclusion: High dose cytarabine combined with zenubrutinib was effective and well-tolerated in patients with relapsed/refractory PCNSL.

No relevant conflicts of interest to declare.

Zenubrutinibï¼Å'which is designed to treat mantle cell lymphoma or small lymphocytic lymphoma, was used to treat primary central nervous system lymphoma in the trial.