Work

High level of anti-drug antibodies is associated with shorter survival in advanced solid cancer patients treated with Immune checkpoint inhibitors

Year: 2024

Type: article

Abstract: Background Camrelizumab has become the first-line treatment for most patients with advanced tumors. Among advanced tumor patients undergoing camrelizumab, the majority develop immunogenicity, resulting in the production of anti-drug antibodies (ADA). The impact of ADA on the efficacy and safety of camrelizumab treatment is currently unknown. Method Hematologic samples from 31 tumor patients treated with camrelizumab were collected to serve as an experimental cohort for ADA levels detection. Concurrently, a separate validation cohort consisting of 16 patients was established. Follow-up data on patients’ OS and PFS were collected and analyzed. Results High ADA levels (≥1200 ng/ml) after the three cycles camrelizumab treatment were linked to poorer patient outcomes, as shown by significant differences between PD and PR (P = 0016) and PR and SD (P = .0439). This trend was also present in the validation cohort (PD vs PR, P = .0413). More importantly, high ADA levels after the three cycles camrelizumab treatment were associated with a significant reduction in OS (P = .0128) and PFS (P = .0004), with the validation cohort reporting comparable findings (OS: P = .0009; PFS: P = .0007). Additionally, camrelizumab concentration was negatively correlated with ADA levels (experimental cohort: R2 = 0.3876; validation cohort: R2 = 0.3702). Patients had higher ADA levels after the early phase of camrelizumab treatment. Conclusion High ADA levels were associated with shorter OS and PFS in patients after three cycles of camrelizumab therapy. Furthermore, patients had higher ADA levels after the early phase of treatment, specifically in the first three cycles with camrelizumab. It found that the higher the ADA concentration, the lower the serum camrelizumab concentration.

Source: Immunotherapy Advances

DOI: 10.1093/immadv/ltaf019