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:The impact of race, ethnicity, and obesity on CAR T-cell therapy outcomes.
The impact of race, ethnicity, and obesity on CAR T-cell therapy outcomes.
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化疗治疗少数族裔患者和肥胖患者的癌症结局较差。嵌合抗原受体(CAR)T细胞疗法改善了复发/难治性血液系统恶性肿瘤结局,但其获益是否同样惠及少数族裔和肥胖患者,尚不清楚。
本研究重点关注B细胞急性淋巴细胞白血病(B-ALL),回顾性评估美国国家癌症研究所2012年至2021年5项I期临床试验中,接受CAR-T 细胞治疗的成人和儿童血液系统恶性肿瘤患者的人口学特征及肥胖对治疗结局的影响。在139次B-ALL CAR-T 输注中,患者28.8%为西班牙裔、3.6%为黑人、29.5%为超重/肥胖。种族、族裔或体重指数(BMI)与完全缓解率、神经毒性或总生存期均无显著相关性。即使调整白血病疾病负荷和年龄后,与非西班牙裔白人患者相比,西班牙裔患者更可能发生重度细胞因子释放综合征(优势比4.5;P=0.001)。多发性骨髓瘤(n=24)和非霍奇金淋巴瘤(n=23)患者的描述性分析显示了与B-ALL队列类似的模式。
研究发现提示,CAR-T 治疗可能对不同人口学特征群体均有显著获益,包括化疗耐药和复发风险较高的人群。然而,毒性谱可能存在差异。
因此,应优先改善代表性不足人群获得CAR治疗的机会,并阐明不同人口学群体毒性差异的机制。
Cancer outcomes with chemotherapy are inferior in patients of minority racial/ethnic groups and those with obesity. Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for relapsed/refractory hematologic malignancies, but whether its benefits extend commensurately to racial/ethnic minorities and patients with obesity is poorly understood. With a primary focus on patients with B-cell acute lymphoblastic leukemia (B-ALL), we retrospectively evaluated the impact of demographics and obesity on CAR T-cell therapy outcomes in adult and pediatric patients with hematologic malignancies treated with CAR T-cell therapy across 5 phase 1 clinical trials at the National Cancer Institute from 2012 to 2021.
Among 139 B-ALL CAR T-cell infusions, 28. 8% of patients were Hispanic, 3. 6% were Black, and 29. 5% were overweight/obese. No significant associations were found between race, ethnicity, or body mass index (BMI) and complete remission rates, neurotoxicity, or overall survival.
Hispanic patients were more likely to experience severe cytokine release syndrome compared with White non-Hispanic patients even after adjusting for leukemia disease burden and age (odds ratio, 4. 5; P = . 001). A descriptive analysis of patients with multiple myeloma (n = 24) and non-Hodgkin lymphoma (n = 23) displayed a similar pattern to the B-ALL cohort.
Our findings suggest CAR T-cell therapy may provide substantial benefit across a range of demographics characteristics, including for those populations who are at higher risk for chemotherapy resistance and relapse.
However, toxicity profiles may vary. Therefore, efforts to improve access to CAR therapy for underrepresented populations and elucidate mechanisms of differential toxicity among demographic groups should be prioritized.
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