不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CD19 expression is preserved following CD19-directed monoclonal antibody therapy with tafasitamab.
CD19 expression is preserved following CD19-directed monoclonal antibody therapy with tafasitamab.
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这些数据提示,tafasitamab 治疗即使在最近一线使用,也可能不排除后续使用其他 CD19 靶向药物。
CD19靶向治疗后可能消除或降低CD19表达的风险,引发了关于B细胞恶性肿瘤最佳治疗顺序策略的疑问。本研究评估了接受tafasitamab(一种抗CD19单克隆抗体)治疗的复发/难治性B细胞恶性肿瘤患者样本中的CD19表达和突变状态。
从一项临床试验或真实世界环境中接受tafasitamab治疗的共计100例复发/难治性B细胞恶性肿瘤患者中收集了活检和外周血样本。来自66例患者的治疗后样本可用于评估CD19蛋白表达;由于缺乏残留淋巴瘤细胞而无法评估CD19表达,6份样本被排除在分析之外。其余60份样本通过免疫组织化学(n=46)或流式细胞术(n=14)进行评估。下一代测序(NGS)用于评估CD19突变状态(n=39)和转录本表达(n=4)。通过免疫组织化学和流式细胞术评估了用tafasitamab处理的淋巴瘤细胞系中CD19的保留情况。
在通过免疫组织化学评估的46份患者样本中,45份(98%)在tafasitamab治疗后呈CD19阳性。通过流式细胞术分析的所有14份样本中CD19表达均得以保留。39份样本的NGS未发现体细胞CD19突变。通过流式细胞术评估时,经tafasitamab治疗的淋巴瘤细胞中CD19表达被短暂遮蔽;然而,在所有评估时间点,通过免疫组织化学均可检测到表达。
Biopsy and peripheral blood samples were collected from a total of 100 patients with relapsed or refractory B-cell malignancies who received tafasitamab in a clinical trial or a real-world setting. Post-treatment samples collected from 66 patients were available for assessment of CD19 protein expression; six samples were excluded from the analyses as CD19 expression could not be assessed due to lack of residual lymphoma cells. The remaining 60 samples were assessed by either immunohistochemistry (n=46) or flow cytometry (n=14). Next-generation sequencing (NGS) was used to assess CD19 mutational status (n=39) and transcript expression (n=4). CD19 retention in lymphoma cell lines treated with tafasitamab was assessed by immunohistochemistry and flow cytometry.
Of 46 patient samples assessed by immunohistochemistry, 45 (98%) were CD19 positive after tafasitamab treatment. CD19 expression was retained in all 14 samples analyzed by flow cytometry. NGS of 39 samples revealed no somatic CD19 mutations. CD19 expression was transiently masked in lymphoma cells treated with tafasitamab when assessed by flow cytometry; however, expression was detectable by immunohistochemistry at all time points assessed.
These data suggest that tafasitamab treatment, even in the most recent line, may not preclude subsequent treatment with other CD19-targeting agents.
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