决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Patient-reported outcomes in CD30-directed CAR-T cells against relapsed/refractory CD30+ lymphomas.
Patient-reported outcomes in CD30-directed CAR-T cells against relapsed/refractory CD30+ lymphomas.
我们比较了采集前、输注时和输注后4周时的PROMIS评分及总体症状负担。
靶向CD30的嵌合抗原受体(CAR)-T细胞在复发/难治性CD30+血液系统恶性肿瘤患者中,尤其是在经典型霍奇金淋巴瘤患者中,已显示出高缓解率,并在部分患者中观察到持久缓解。该疗法毒性发生率低,包括细胞因子释放综合征,且在我们的2期研究中未观察到神经毒性。我们收集了接受CD30靶向CAR-T细胞治疗患者的患者报告结局(PROs),以评估该疗法对其症状体验的影响。我们在CD30靶向CAR-T细胞临床试验入组患者中,于采集时、CAR-T细胞输注时以及治疗后多个时间点收集了PROs,包括PROMIS(患者报告结局测量信息系统)全球健康和躯体功能问卷,以及选自NCI PRO-CTCAE的部分症状问题。我们比较了采集前、输注时和输注后4周时的PROMIS评分和总体症状负担。在28例入组患者中,有23例在研究期间至少完成了一次PRO测量。在CAR-T细胞输注后4周时,患者总体症状负担、全球健康和心理 health 以及躯体功能达到或高于基线水平。此外,参与该临床试验患者的PROMIS评分与平均健康人群相似。CD30 CAR-T细胞疗法具有有利的毒性特征,患者躯体功能和症状负担在输注后1个月时恢复至至少其治疗前基线健康水平。试验注册号:NCT02690545。
Chimeric antigen receptor (CAR)-T cells targeting CD30 have demonstrated high response rates with durable remissions observed in a subset of patients with relapsed/refractory CD30+ hematologic malignancies, particularly classical Hodgkin lymphoma. This therapy has low rates of toxicity including cytokine release syndrome with no neurotoxicity observed in our phase 2 study. We collected patient-reported outcomes (PROs) on patients treated with CD30 directed CAR-T cells to evaluate the impact of this therapy on their symptom experience. We collected PROs including PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health and Physical Function questionnaires and selected symptom questions from the NCI PRO-CTCAE in patients enrolled on our clinical trial of CD30-directed CAR-T cells at procurement, at time of CAR-T cell infusion, and at various time points post treatment. We compared PROMIS scores and overall symptom burden between pre-procurement, time of infusion, and at 4 weeks post infusion. At least one PRO measurement during the study period was found in 23 out of the 28 enrolled patients. Patient overall symptom burden, global health and mental health, and physical function were at or above baseline levels at 4 weeks post CAR-T cell infusion. In addition, PROMIS scores for patients who participated in the clinical trial were similar to the average healthy population. CD30 CAR-T cell therapy has a favorable toxicity profile with patient physical function and symptom burden recovering to at least their baseline pretreatment health by 1 month post infusion. Trial registration number: NCT02690545.
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