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:CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study.
CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study.
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我们队列中输注后 3 个月的低缓解率主要受大肿块疾病影响。需要进一步研究以更好地描述 CAR-T 细胞疗效丧失的特征,因为大多数患者会随时间推移而复发。
嵌合抗原受体(CAR)T细胞是治疗大B细胞淋巴瘤(LBCL)的重要新型三线治疗选择。在关键的早期临床试验中,CAR-T 细胞的客观缓解率非常令人鼓舞。本研究的目的是描述我们机构中输注CAR-T 细胞所获得的疗效结果,并将我们队列的毒性与关键试验及真实世界环境中进行的研究中的毒性进行比较。
在CHU de Québec-Université Laval,回顾性收集了25例接受CAR-T 细胞治疗的LBCL患者的疗效和安全性数据。随后进行了文献检索,以识别来自真实世界的其他疗效或安全性数据。
输注后3个月,我们人群中接受tisagenlecleucel和axicabtagene-ciloleucel治疗的客观缓解率(ORR)分别为20%和47%。大包块疾病是3个月时缓解不佳的唯一阴性预测因素(0% vs. 53%,P = .03)。大包块疾病与中位PFS 2个月相关,而非大包块疾病为5个月(P = .0009)。3级血液学毒性在接受axi-cel治疗的患者中更高(60% vs. 20%,P = .048),在无骨髓受累的患者中更高(55% vs. 0%,P = .046),在无IV期疾病的患者中更高(72% vs. 21%,P = .02),在难治性疾病的患者中更高(67% vs. 10%,P = .01),或在发生细胞因子释放综合征的患者中更高(58% vs. 0%,P = .02)。
Chimeric antigen receptor (CAR) T-cells are an important new third-line treatment option for large B-cell lymphoma (LBCL). The objective response rates in pivotal early phase clinical trials with CAR T-cells were very promising. The objective of this study was to describe the efficacy results obtained with CAR T-cells infusions in our institution and to compare the toxicities of our cohort with those of pivotal trials and studies conducted in a real-life setting.
Efficacy and safety data were retrospectively collected from 25 patients with LBCL treated with CAR T-cells therapy at CHU de Qu bec-Universit Laval. A literature search was then performed to identify other efficacy or safety data from a real-life setting.
At 3 months post infusion, the objective response rate (ORR) in our population with tisagenlecleucel and axicabtagene-ciloleucel were 20% and 47%, respectively. Bulky disease was the only negative predictor of poor response at 3 months (0% vs. 53%, P = .03). Bulky disease was associated with a median PFS of 2 months compared to 5 months for non-bulky disease (P = .0009). Grade 3 hematological toxicities were greater in patients treated with axi-cel (60% vs. 20%, P = .048), without bone marrow involvement (55% vs. 0%, P =.046), without stage IV disease (72% vs. 21%, P =.02), with refractory disease (67% vs. 10%, P =.01) or having been affected by cytokine release syndrome (58% vs. 0%, P =.02).
The poor response rate at 3 months after infusion in our cohort was influenced mainly by bulky disease. Further studies are needed to better characterize the loss of efficacy of CAR T-cells because the majority of patients will relapse over time.
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