Smart start with tislelizumab as the front‐line treatment in patients with high‐risk stage iib and advanced‐stage classical hodgkin lymphoma

Introduction: Around 10%–30% of classical Hodgkin's lymphoma(cHL) will relapse or refract after treatment with traditional cytotoxic drug-based chemotherapy, meanwhile the chemotherapy-related toxicity cannot be ignored. In order to balance efficacy and toxicity, we use the concept of ‘Smart Start’ to explore the efficacy and safety of tislelizumab sequentially combined with AVD regimen in the first-line treatment of cHL in phase II study (NCT04843267). Method: The study included untreated cHL patients with advanced-stage (III–IV and IIB with unfavorable risk factors). All patients first received 2 cycles of tislelizumab monotherapy and then entered into the PET-CT evaluation (PET-2). According to PET-2, complete response (CR) patients continued to receive 4 cycles of tislelizumab monotherapy, partial response (PR) patients received 4 cycles of tislelizumab and AVD combination therapy, progression disease (PD)/stable disease (SD) patients withdrew from the study. After 6 cycles of the treatment, the patients who still maintained PR according to the PET-CT evaluation (PET-3), could receive 2 additional cycles of tislelizumab and AVD combination therapy. The primary endpoint is the CR rate in PET-2, and the secondary endpoints include overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. Results: 29 patients were enrolled in this study till 27 February 2023. Among them one patient was removed due to pathological review as peripheral T-cell lymphoma. The basic characteristics of the 28 patients who met the inclusion criteria are shown in Table 1. The median age was 34y (21–68), stage IIB 10.7%, stage III 25.0%, stage IV 64.3%. All 28 patients have received at least two cycles of tislelizumab monotherapy and PET-2 efficacy evaluation, the swimming plot of efficacy and overall survival were shown in Figure 1. After PET-2, the CR rate was 28.6% (8/28), the overall response rate (ORR) was 96.4% (27/28), and one patient (3.6%) developed PD. Up to PET-3, 21 patients completed all treatment, the other 7 were still in the treatment. 19 patients (90.5%,19/21) achieved CR, one (4.8%) achieved PR, and one (4.8%) had PD during the treatment, with the ORR of 95.2%. During the follow-up, six of the 8 CR patients in PET-2 had still maintained CR after 6 cycles of tislelizumab monotherapy without chemotherapy. The safety profile was shown in Table 2. The study was well tolerated, and there was no treatment-related SAE or death. Immune-related AEs were mostly concentrated in grade 1/2, and grade 3/4 hematological toxicities were mainly happened during the combination treatment period. Keywords: Hodgkin lymphoma, immunotherapy No conflicts of interests pertinent to the abstract.