Phase II Clinical Trial of Camrelizumab Combined with AVD (Epirubicin, Vincristine and Dacarbazine) in the First-Line Treatment for Patients with Advanced Classical Hodgkin's Lymphoma

Background Hodgkin Lymphoma (HL) is a kind of malignant tumor of the lymph system, approximately 95% of which are classical Hodgkin's lymphoma (cHL). ABVD and BEACOPP regimens are commonly used first-line induction treatment regimens for cHL. Sequential radiotherapy for residual lesions or large masses is the current standard treatment after remission. However, disease relapse or drug resistance still occurs in approximately one third of patients, mainly in patients with advanced disease, including Ann Arbor stage III/IV, stage II with B symptoms, and large mediastinal mass or extranodal lesions. Studies have found that the PD-1/PD-L1 pathway plays an important role in the development of cHL disease. Blocking the signaling of the PD-1/PD-L1 pathway may relieve immunosuppression and promote the clearance of RS cells by the immune system. Camrelizumab, a humanized anti-PD-1 IgG4 monoclonal antibody, is independently developed in China. The goal of our trial is to assess the efficacy and safety of Camrelizumab combined with AVD (Epirubicin, Vincristine and Dacarbazine) in the first-line treatment for patients with advanced classical Hodgkin's lymphoma.

Methods The patients received 6 cycles of Camrelizumab combined with AVD regimen as first-line therapy. The primary endpoint was objective response rate (ORR), including complete remission (CR) and partial remission (PR), and secondary endpoints were 2-year progression-free survival (PFS), overall survival (OS) and safety. Exploratory endpoints: efficacy and international prognostic score (IPS), hotspot driver gene mutations, characteristic expression (PDL1, BCL2, c-MYC, P53, CD10, BCL6, MUM1/IRF4, and EBER) of tumor cells (RS cells), and correlation of tumor microenvironment and cytokines.

Results From September 15, 2019 to June 15, 2022, a total of 20 patients were enrolled, including 4 patients (20%) in stage II, 7 patients (35%) in stage III, and 9 patients (45%) in stage IV; 11 cases (55%) with B symptoms; 1 case (1/16) with IPS score of 0, 5 cases (5/16) with IPS score of 1, 6 cases (6/16) with IPS score of 2, and 2 cases (2/16) with IPS score of 3, and 2 cases (2/16) with IPS score of 4; EBER was positive in 8 cases (40%); lymphoma-related 93 gene detection was performed in 7 cases (35%). At present, 17 patients had completed all the treatments, and the final response of 15 patients had reached CR (88.2%) and 2 patients PR (11.8%). 2-year PFS has not been reached. The combination regimens were well tolerated. Among the 17 patients who had completed all treatments, the common adverse events of treatment were reactive cutaneous capillary endothelial proliferation (RCCEP) in 8 cases (47.1%), gastrointestinal reaction in 6 cases (35.3%), peripheral neuropathy in 4 cases (23.5%), hypothyroidism in 3 cases (17.6%), rash in 2 cases (11.8%), increased AST/ALT levels in 2 cases (11.8%), pneumonitis in 1 case (5.9%), and all of which were grade 1-2. 2 cases of liver function damage was grade 3 (11.8%).

Conclusion Camrelizumab combined with AVD has a good effect in the first-line treatment for advanced classical Hodgkin lymphoma, with an objective response rate (ORR) of 100%, and the patients are well tolerated.

No relevant conflicts of interest to declare.

Camrelizumab, a humanized anti-PD-1 IgG4 monoclonal antibody, is independently developed in China. It is indicated for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma after at least second-line systemic chemotherapy. The goal of our trial is to assess the efficacy and safety of Camrelizumab combined with AVD in the first-line treatment for patients with advanced classical Hodgkin's lymphoma.