合并用药对晚期胃癌 CLDN18.2 特异性 CAR-T 细胞治疗疗效的影响

Claudin18.2 (CLDN18.2)-specific CAR-T cell therapy has demonstrated promise in advanced gastric cancer (GC). However, the impact of concomitant medications on the efficacy outcomes remains unclear.

We retrospectively analyzed advanced GC patients receiving CLDN18.2-specific CAR-T cell therapy from a phase I trial. Concomitant medications were defined as any drugs administered within 30 days before and after CAR-T cell infusion, including corticosteroids, antibiotics, tocilizumab, granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and erythropoietin. Metagenomic sequencing was employed to elucidate the differences in gut microbiome signatures between responders and non-responders.

Of 72 patients included in the study, 6 (8.3%) received corticosteroids, 49 (68.1%) received tocilizumab, and 22 (30.6%) received antibiotics, 15 (20.8%) received G-CSF, 5 (6.9%) received thrombopoietin, and no patient received erythropoietin. The median progression-free survival (PFS) (2.6 vs. 5.8 months; P < 0.001) and overall survival (OS) (3.9 vs. 9.5 months; P < 0.001) were significantly shorter for patients who received antibiotics for infection compared to those who did not. No significant differences were observed in objective response rate (ORR), PFS, and OS between patients who received corticosteroids, tocilizumab, antibiotics for prophylaxis, G-CSF, or TPO and those who did not. A higher abundance of Fusobacterium nucleatum, Lactobacillus mucosae, Prevotella pallens, and Streptococcus pseudopneumoniae in gut microbiome was associated with a superior treatment response.

The study indicates that the use of antibiotics for infection reduces the efficacy outcomes of CLDN18.2-specific CAR-T cell therapy for advanced GC, while other concomitant medications do not affect the outcomes. Further research is needed to clarify the optimal administration of these medications and the underlying mechanisms of the gut microbiome in impacting CAR-T treatment response. TRIAL REGISTRATION: NCT03874897.