The role of extranodal (EN) sites as potential sanctuary regions resistant to CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) remains unclear. To investigate this, we retrospectively analyzed 283 adults treated with commercial CD19 CAR-T therapy, assessing 958 PET-CT scans across four time points: pre-apheresis, pre-lymphodepletion, best response, and relapse. EN involvement prior to CAR-T therapy was common (76%). Outcomes for patients with exclusive EN disease were similar to those with nodal (ND) disease alone; however, patients with concomitant EN and ND disease (EN + ND) had lower complete response rates and shorter progression-free survival. Site-specific outcomes varied: lungs/pleura/pericardium and gastrointestinal/peritoneum involvement had the lowest local response rates (48% and 51%, respectively). Notably, the risk of same-site relapse was highest in the lungs/pleura/pericardium (hazard ratio [HR] 7.8) and gastrointestinal/peritoneum (HR 5.97). Among patients relapsing after CAR-T, two-year overall survival rates from time of relapse were significantly lower in those with EN relapse (23% for exclusive EN; 25% for EN + ND) compared to exclusive ND relapse (64%; p = 0.008). These findings underscore the high prevalence of EN disease in CAR-T recipients and its site-specific impact on outcomes, highlighting the need for organ-targeted strategies to enhance treatment efficacy. Differential site-specific response and relapse/progression risk according to pre-CAR-T therapy anatomical site involvement in Large B-cell Lymphoma. Risk of site-specific relapse or progression was not evaluable for CNS/orbital/cranial sinuses, adrenal/genitourinary, hepatobiliary/pancreas, and spleen due to insufficient number of events.
结外（EN）部位作为大B细胞淋巴瘤（LBCL）中可能抵抗CD19靶向嵌合抗原受体T细胞（CAR-T）疗法的庇护区域，其作用尚不明确。为探究此问题，我们回顾性分析了283例接受商业化CD19 CAR-T治疗的成年患者，评估了四个时间点的958次PET-CT扫描：单采前、淋巴细胞清除前、最佳应答时及复发时。CAR-T治疗前结外受累很常见（76%）。单纯结外疾病患者的结局与单纯淋巴结（ND）疾病患者相似；然而，同时存在结外和淋巴结疾病（EN+ND）的患者完全缓解率更低，无进展生存期更短。不同部位的结局存在差异：肺/胸膜/心包和胃肠道/腹膜受累的局部缓解率最低（分别为48%和51%）。值得注意的是，同一部位复发风险最高的是肺/胸膜/心包（风险比[HR] 7.8）和胃肠道/腹膜（HR 5.97）。在CAR-T治疗后复发的患者中，结外复发患者自复发起的两年总生存率（单纯结外复发为23%；EN+ND复发为25%）显著低于单纯淋巴结复发患者（64%；p=0.008）。这些发现强调了结外疾病在CAR-T接受者中的高发性及其对结局的特定部位影响，凸显了需要针对器官的策略以提高治疗效果。根据大B细胞淋巴瘤患者接受CAR-T治疗前解剖部位受累情况，不同部位的应答及复发/进展风险存在差异。中枢神经系统/眼眶/颅窦、肾上腺/泌尿生殖系统、肝胆/胰腺和脾脏因事件数量不足，无法评估其特定部位复发或进展的风险。
CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma
肿瘤(癌症)患者之家