CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects.

Systemic administration of immunotherapy via intravenous injection is frequently associated with off-target toxicity throughout the body. In contrast, intratumoral injection has emerged as a promising strategy to mitigate systemic adverse effects. However, data regarding the safety of CT-guided intratumoral immunotherapy remain limited. This pooled prospective cohort study included patients from several single-arm clinical trials. Eligible participants had histologically confirmed advanced solid tumors that were refractory or intolerant to standard therapies. Each participant had at least one measurable tumor lesion accessible for puncture under imaging guidance. All patients received CT-guided intratumoral injection of various ICIs (PD-1, PD-L1, and CTLA-4 inhibitors) either alone or in combination, or of CAR-T cells. The primary endpoint was safety of the treatment. A total of 169 patients were included in the study cohort, with a median follow-up duration of 8.4 months (range, 1.0-38.0 months). Grade 3-4 adverse events occurred in 15 patients (8.88%), comprising 10 (5.92%) grade 3 and 5 (2.96%) grade 4 events; no treatment-related deaths were observed. Efficacy outcomes included 4 patients (2.37%) with complete response (CR), 15 (8.88%) with partial response (PR), 142 (84.02%) with stable disease (SD), and 8 (4.73%) with progressive disease (PD). The objective response rate (ORR) was 11.24%, and the disease control rate (DCR) was 95.27%. The median progression-free survival (PFS) was 3.6 months (95% CI, 3.1-4.1 months), and the median overall survival (OS) was 8.8 months (95% CI, 8.2-9.3 months). This study indicates the safety and preliminary therapeutic potential of intratumoral injection. Intratumoral injection may be a promising strategy for mitigating systemic toxicity; however, further research is necessary to validate its therapeutic efficacy. https://clinicaltrials.gov, identifier NCT03198052, NCT03769129, NCT03755739, NCT03952065, and NCT05341492.