The safety and efficacy of chimeric antigen receptor-T cell therapy in solid malignancies: a systematic review and meta-analysis

Abstract

Introduction Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in hematologic malignancies, prompting its exploration in solid tumors. This systematic review and meta-analysis aimed to evaluate the safety and feasibility of CAR-T therapy for solid tumor treatment. Methods We systematically searched PubMed, Cochrane Library, Embase, and Web of Science from database inception to June 1, 2026, for clinical studies evaluating CAR-T therapy in solid tumors. Primary outcomes included the incidence of any-grade and grade ≥3 adverse events (AEs); secondary outcomes were the overall response rate (ORR) and disease control rate (DCR). This review adhered to PRISMA guidelines and was registered with PROSPERO (CRD42024549048). Results 52 studies with 712 patients were enrolled in our study. Lymphopenia (70%, grade≥3: 48%) was the most common adverse event. The pooled ORR and DCR were 13% (95%CI: 11-16%) and 63% (95%CI: 59-67%), respectively. Subgroup analysis indicated that the incidence of hematologic toxicity was significantly higher in patients who had received lymphodepletion, and intravenous delivery was associated with a higher risk of several AEs. Patients who had undergone lymphodepletion (LD) achieved higher ORR (p = 0.0002) and DCR (p = 0.0083). In comparison to regional delivery, intravenous infusion was associated with higher ORR (p = 0.0345). Conclusion CAR-T therapy demonstrates an acceptable safety profile for solid tumors. While lymphodepletion and intravenous delivery correlate with higher ORR and DCR, they also increase adverse event risks. Balancing therapeutic benefits and safety concerns therefore remains a critical consideration for clinical practice.