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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Patterns of Utilization and Outcomes of Autologous Stem Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements.
Patterns of Utilization and Outcomes of Autologous Stem Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements.
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复发双打击/三打击淋巴瘤的真实世界总生存期劣于非双打击/三打击淋巴瘤。
伴MYC及BCL2和/或BCL6基因重排的弥漫大B细胞淋巴瘤(DLBCL)患者,即双重打击/三重打击淋巴瘤(DHL/THL),在复发/难治阶段预后较差。
利用DLBCL患者去标识化真实世界数据库,报告复发/难治性DLBCL的治疗使用模式。按既往治疗线数分层,采用log-rank检验比较DHL与非DHL亚组接受CAR-T 细胞治疗或自体造血干细胞移植(ASCT)后的真实世界总生存期(rwOS)。
7877例DLBCL患者中,367例为DHL,6113例为非DHL。147例DHL和1517例非DHL患者接受二线化疗。另排除1393例,其中934例DHL/THL状态未知。DHL亚组约47%接受挽救性化疗,其中19%最终接受ASCT;非DHL/THL组34%接受挽救性化疗,其中32%接受ASCT。DHL/THL状态会降低接受二线ASCT患者的中位rwOS;在多变量分析中,该状态与接受CAR-T 细胞治疗患者数值上较差但无统计学显著差异的rwOS相关。
复发DHL/THL患者rwOS差于非DHL/THL患者。与非DHL/THL相比,挽救化疗后能够继续接受ASCT的DHL/THL患者更少。复发DHL/THL患者二线ASCT后的rwOS差于非DHL/THL患者,这与DHL/THL的自然病程一致。CAR-T 治疗未观察到这一差异;结合临床试验中的良好结果,提示CAR-T 细胞疗法在复发/难治性DHL中可能具有更重要的作用。
Patients with Diffuse Large Bcell Lymphoma (DLBCL) with MYC and BCL2 and/or BCL6 gene rearrangements [double-hit lymphoma/triple-hit lymphoma (DHL/THL)] have poor prognosis in the relapsed/refractory setting.
We utilized a real-world deidentified database of DLBCL patients and report patterns of therapy utilization in relapsed/refractory DLBCL. We used log-rank test to compare real-world overall survival (rwOS) among DHL and non-DHL subgroups for CAR Tcell therapy or ASCT respectively, stratified for prior lines of therapy.
Of all 7,877 patients with DLBCL, 367 patients had DHL while 6113 had non-DHL. Second line chemotherapy was administered to 147 DHL patients and 1517 non-DHL. 1393 were excluded, including 934 with unknown DHL/THL status. Approximately 47% received salvage intent chemotherapy in the DHL subgroup, of which 19% patients eventually received ASCT, while 34% received salvage intent chemotherapy in the non-DHL/THL group with 32% receiving ASCT. DHL/THL status negatively influenced median rwOS for patients who underwent ASCT in the second-line while it was associated with numerically inferior but without statistically significant rwOS among patients that underwent CAR Tcell therapy on multivariable analysis.
rwOS of relapsed DHL/THL is inferior to non-DHL/THL. Fewer patients with DHL/THL were able to proceed with ASCT after salvage chemotherapy compared to non-DHL/THL. ASCT as second-line therapy for relapsed DHL/THL had worse rwOS than for non-DHL/THL, consistent with the natural history of DHL/THL. This difference was not seen for CAR Tcell therapy, which combined with promising results from clinical trials, suggests a greater role for CAR T-cell therapy in relapsed/refractory DHL.
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