CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy.
Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy.
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若在大型患者队列中得到证实,这些发现可为修改当前的患者选择标准奠定基础。
引言:由于免疫组织化学(IHC)或流式细胞术存在局限,目前指南未要求大 B 细胞淋巴瘤(LBCL)患者在接受CAR-T 细胞疗法前评估肿瘤 CD19 表达。定量聚合酶链式反应(qPCR)检测 CD19 表达的灵敏度更高,其主要优势是可从石蜡包埋组织中轻易提取 mRNA。方法与结果:研究纳入 51 例接受 axicabtagene ciloleucel 治疗的成年 LBCL 患者。其中 16 例经 IHC 判定为 CD19 阴性,但 qPCR 将其中 6 例(37.5%)重新判定为 CD19 阳性。研究者比较持续 CD19 阴性(IHC−、qPCR−)患者与 CD19 阳性患者(IHC+,或 IHC−且 qPCR+)的结局。CD19 阴性组的 1 年无进展生存率更差(15% 对 45%,p = 0.044),缓解持续时间也呈缩短趋势(29% 对 55%,p = 0.065)。CD19 阴性患者中仅 1 例(10%)在末次随访时(6 个月)仍存活且无疾病,此患者此前曾对桥接治疗应答。讨论:若能在更大患者队列中证实这些发现,或可据此修改当前患者选择标准。持续 CD19 阴性患者可能不是抗 CD19 CAR-T 治疗的理想候选者;可考虑双特异性抗体或基于 polatuzumab 的方案等替代疗法。
INTRODUCTION: Current guidelines do not mandate CD19 tumor expression assessment before chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) patients due to limitations of immunohistochemistry (IHC) or flow cytometry. Quantitative polymerase chain reaction (qPCR) offers a more sensitive alternative for detecting CD19 expression, with the primary advantage that mRNA can be easily extracted from paraffin-embedded tissues. METHODS & RESULTS: In our study, we included 51 adult patients with LBCL treated with axicabtagene ciloleucel. Among them, 16 were classified as CD19-negative by IHC; however, qPCR reclassified six (37.5%) as CD19-positive. We then compared the outcomes between consistently CD19-negative (IHC - qPCR - ) and CD19-positive (IHC + and IHC - qPCR + ) patients. CD19-negative cohort showed worse 1-year progression-free survival (15 vs. 45%, p = 0.044) and a trend toward shorter duration of response (29 vs. 55%, p = 0.065). Only one (10%) of the CD19-negative patients remained alive and disease-free at last follow-up (6 months), having previously responded to bridge therapy. DISCUSSION: If confirmed in a large patient cohort, these findings could form the basis for modifying current patient selection criteria. Consistently negative patients may be suboptimal candidates for anti-CD19 CAR-T therapy. Alternative therapeutic options, such as bispecific antibodies or polatuzumab-based regimens, could be considered for this subset of patients.
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