Porpaczy Edit, Wohlfarth Philipp, Königsbrügge Oliver, Rabitsch Werner, Skrabs Cathrin, Staber Philipp, Worel Nina, Müllauer Leonhard, Simonitsch-Klupp Ingrid, Kornauth Christoph, Rohrbeck Johannes, Jaeger Ulrich, Schiefer Ana-Iris
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Internal Medicine I, Hematopoietic Stem Cell Transplantation Unit, Medical University of Vienna, 1090 Vienna, Austria.
Cancers (Basel). 2021 Nov 9;13(22):5592. doi: 10.3390/cancers13225592.
Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient's own immune system to kill the tumor cells. We investigated the impact of mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with and/or rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, mutation was an independent prognostic factor for overall survival (OS) (median 12 months with vs. not reached without mutation, < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, = 0.263). The findings from this monocentric retrospective study indicate that mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.
难治性/复发性弥漫性大B细胞淋巴瘤（DLBCL）预后较差。DLBCL的临床行为和基因图谱具有异质性，目前仍未完全了解。DLBCL中的 突变已被确定为预后不良的标志物，且常与治疗耐药相关。嵌合抗原受体T细胞疗法是一种创新的治疗理念，通过支持患者自身免疫系统杀死肿瘤细胞，代表了一种改变治疗格局的治疗选择。我们研究了 突变对接受相似治疗线数的难治性/复发性DLBCL患者总生存的影响。治疗线数的最小值为2（中位数为4），包括抗CD19嵌合抗原受体T细胞疗法或传统挽救疗法。纳入了2000年至2021年期间在我院诊断和治疗的170例患有 重排和/或 重排的DLBCL及高级别B细胞淋巴瘤（DHL/THL）患者。其中29例接受了嵌合抗原受体T细胞疗法。嵌合抗原受体T细胞组和传统组分别有10/29（35%）和31/141（22%）的患者检测到 突变。在141例未接受嵌合抗原受体T细胞治疗的患者中， 突变是总生存（OS）的独立预后因素（有 突变者的中位OS为12个月，无 突变者未达到， <0.005），但在接受嵌合抗原受体T细胞治疗的组中，未显示出这种显著性（中位OS分别为30个月和120个月， =0.263）。这项单中心回顾性研究的结果表明， 突变状态似乎不影响接受嵌合抗原受体T细胞疗法治疗的DLBCL患者的预后。有必要在大型队列中进行详细评估。
