P1119: camrelizumab plus low-dose apatinib and pegaspargase followed by radiotherapy for newly diagnosed stage i/ii natural killer/t-cell lymphoma: a prospective multicenter single-arm study

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Immune checkpoint blockade has been demonstrated to be feasible in patients with natural killer/T-cell lymphoma (NK/TCL). Camrelizumab, a PD-1 blockade, has shown promising anti-tumor activity and acceptable toxicity in several solid tumors and lymphomas. Apatinib is an oral tyrosine kinase inhibitor that inhibits tumor angiogenesis by selectively targeting VEGFR-2, which has also been evaluated in lymphomas. The combination of camrelizumab with low-dose apatinib had a synergistic effect, which showed promising results in patients with solid tumors. Aims: This study aimed to evaluate the efficacy and safety of camrelizumab in combination of low-dose apatinib and pegaspargase followed by radiotherapy for newly diagnosed stage I/II NK/TCL. Methods: In this prospective, multicenter, single-arm study, patients with newly diagnosed stage I/II NK/TCL from 3 centers in China were enrolled. The key inclusion criteria were: biopsy-proven NK/TCL according to the World Health Organization classification 2016, newly diagnosed cases with at least one measurable lesion, stage I/II based on Lugano 2014 classification systems, aged 18 to 80 years old, and Eastern Cooperative Oncology Group performance status score of 0 to 2. Eligible patients received four 21-day cycles of intravenous camrelizumab 200 mg on day 1, intramuscular pegaspargase 2000 U/m2 on day 1, and oral apatinib 250 mg daily. A total dose of 50-56 Gy of extended-field radiotherapy was administered within two weeks after systemic therapy. The primary endpoint was complete response rate after radiotherapy (24-week) according to Lugano 2014 criteria. Results: Between May, 2020 and October, 2022, a total of 62 patients were enrolled in this study. The median age of patients was 52 (interquartile range: 36, 61) years old, and 38 (61.3%) were male. Thirty-two patients (51.6%) had stage I disease, while 30 (48.4%) had stage II disease. Totally, 31 patients (50.0%) experienced B symptoms. Six (9.7%) patients had elevated lactate dehydrogenase, and 25 (40.3%) had detectable Epstein-Barr virus DNA at baseline. As of cut-off date of January 31th, 2023, 44 patients were evaluable after four cycles of systemic treatment (12-week). The 12-week complete response rate was 68.2% (95% confidence interval [CI]: 54.4%-81.9%), and the 12-week objective response rate was 81.8% (95%CI: 70.4%-93.2%). Fifty patients were evaluable at 24-week, and one patient died due to disease progression during radiotherapy. A total of 44 patients achieved complete response, and three patients achieved partial response at 24-week, with a complete response rate of 88.0% (95% CI: 79.0%-97.0%) and an objective response rate of 94.0% (95%CI: 87.4%-100%). A total of 60 patients (96.8%) reported treatment-related adverse events (TRAEs), and 29 (46.8%) had grade 3 or higher TRAE. The most common grade 3 or higher TRAE was hypertriglyceridemia (19.4%), followed by hypertension (14.5%) and pain (9.7%). Four patients (6.5%) discontinued treatment due to TRAE, and four patients (6.5%) experienced serious TRAE (including one patient with blood bilirubin increased, one with dizziness, two with aspartate aminotransferase or alanine aminotransferase increased). Summary/Conclusion: The combination of camrelizumab, low-dose apatinib and pegaspargase followed by radiotherapy was effective in treating patients with newly diagnosed stage I/II NK/TCL, with acceptable safety profiles. Long-term follow-up is ongoing to determine the survival benefits of the regimen.Keywords: Clinical trial, Immune therapy, Anti-angiogenesis, NK-T cells