Treatment of refractory DLBCL still represents a unique area of unmet need. Previous studies have shown synergistic antitumour effects between Bruton’s tyrosine kinase inhibitors (BTKi) and immune checkpoint inhibitors. However, it lacks data of zanubrutinib and tislelizumab. Herein, we present the premilitary results of an ongoing, multicenter, single-arm phase II study designed to assess the safety and efficacy of zanubrutinib in combination with tislelizumab in refractory DLBCL patients.
Adult patients diagnosed with DLBCL, with ECOG performance status 0-3 and adequate organ function, who were refractory to at least the first-line of systemic therapies containing rituximab were eligible. Patients who had been exposed to any PD-1/PD-L1 inhibitors or BTKi prior to enrollment were excluded. Each 21-day treatment cycle comprises daily zanubrutinib (160mg bid, d1-d21) in combination with tislelizumab (200mg once, d1). Treatment repeats in the absence of disease progression or unacceptable toxicity, up to 12 months. The primary endpoint is the overall objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DoR), time to relapse (TTR), progression-free survival (PFS), overall survival (OS), and safety outcomes assessed by the CTCAE 5.0.
From Nov 1, 2020 to Sept 5, 2022, 10 patients (70% of male) were enrolled in the study, with a median (range) age of 60.5 (54-76) years. During a median follow up time of 11.1 months, 3 patients achieved CR, of whom all were of non-germinal center origin, two of primary lymph nodes and one of primary testis. This combination resulted in an ORR of 30% with a DCR of 50%. Median PFS was 4.885 (range, 0.76-22.3) months. Other outcomes were immature and not formally tested. TRAEs observed were neutropenia (1 of 10 patients), thrombocytopenia (1 of 10 patients), and elevated creatine phosphokinase (1 of 10 patients). All TRAEs were grade 1 or 2.
This combination of zanubrutinib and tislelizumab is well-tolerated with promising clinical response in refractory DLBCL patients. Further exploration is still warranted, especially in patients with non-GCB and specific refractory DLBCL at immune-privileged sites.
S. Zhou.
Shanghai Lianxiang Public Welfare Foundation.
All authors have declared no conflicts of interest.