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定量 PCR 评估的 CD19 表达在接受 CAR-T 治疗的淋巴瘤患者中的临床影响

英文原题:Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy.

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Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy.

PubMed 2025/03/19(内容时间) EJHaem Q4 · IF 1.3(JCR 2025)

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研究概要

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。

中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Hernani R、Ventura L、Heras B、Serrano A、Rivada M、Martínez-Ciarpaglini C、Benzaquén A、Ferrer-Lores B
单位
Hematology Department, Hospital Clínico Universitario INCLIVA Biomedical Research Institute Valencia Spain.Spain
期刊
EJHaem2025 Apr
原文标识
PubMed 40110072 · DOI 10.1002/jha2.70015