17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Abstract

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma, which accounts for approximately 30%–40% of all cases of non-Hodgkin lymphoma (NHL). Although 60% of patients can be cured by standard R-CHOP (rituximab plus cyclophosphamide, doxoru bicin, vincristine, and prednisone) as frontline therapy, patients with resistance to primary chemoimmunotherapy have a poor prognosis. It has been well demonstrated that TP53mutations and PD-L1 expression correlate with therapeutic resistance. Accordingly, in our preliminary observation, we found that sintilizumab (a PD-1 inhibitor) exerts remarkable efficacy and acceptable tolerance in PD-L1 expressing patients with relapsed or refractory (R/R) DLBCL. Therefore, we further initiate a clinical trial to investigate if sintilizumab can enhance the efficacy of R-CHOP in untreated DLBCL patients with TP53 mutations and PD-L1 expression. Methods: This randomized, multicenter study performs in at least 10 clinical sites in China. Patients aged 18 years or older with histologically diagnosed with DLBCL, untreated and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 are eligible for inclusion. Patients will receive one cycle of R-CHOP regimen and TP53 status and PD-L1 expression will be examined by PCR and immunohistochemistry (IHC), respectively. Afterwards, patients with TP53 mutations and PD-L1 expression (≥30% by IHC) are randomly assigned (1:1) to receive either sintilimab plus R-CHOP regimen (group A) or R-CHOP only (group B) for 5 cycles, until disease progression, unacceptable toxicity or withdrawal of consent. To avoid the interference of prednisolone, sintilizumab (200mg, every 3 weeks) is administered intravenously at day 10 after chemotherapy. Patients achieving CR in group A will continue to receive sintilizumab for 8 cycles. The primary endpoint of this study is complete response rate (CR) according to Lugano classification. Secondary endpoints include objective response rate (ORR) and 1-year progression free survival (PFS). Tumor measurements are assessed by PET/CT at baseline, at weeks 9 and 18, and then by CT scan every 3 months for 1 year. In addition, blood circulating tumor DNA (ctDNA) and PD-L1 are also under evaluation accordingly. Safety was assessed in all treated patients. The study is registered with www.chictr.org, NCT05280626 and is ongoing. Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, ongoing trials No conflicts of interests pertinent to the abstract.