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
靶向 B 细胞成熟抗原的 CAR-T 细胞疗法对复发/难治性多发性骨髓瘤有效，包括体能状态较差的患者
英文原题：CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status.
查看英文原题
CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status.
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中文摘要
在这项开放标签、单臂、I/II期临床试验中，我们评估了抗B细胞成熟抗原（BCMA）嵌合抗原受体（CAR）-T细胞（HDS269B）疗法在49例复发/难治性多发性骨髓瘤（RRMM）患者中的疗效，其中包括20例东部肿瘤协作组（ECOG）3-4级患者。输注HDS269B（9×10^6 CAR+细胞/kg）后，17例患者（34.69%，11例ECOG 0-2，6例ECOG 3-4）发生细胞因子释放综合征[1-2级：14例（28.57%）；3级：3例（6.12%）]。客观缓解率（ORR）为77%，完全缓解（CR）率为47%。15例患者持续缓解>12个月，其中1例延长至>38个月。
中位无进展生存期（PFS）和总生存期（OS）分别为10个月（95% CI 5.3-14.7）和29个月（95% CI 10.0-48.0）。PFS（12个月）率和OS（18个月）率分别为41.64%和62.76%。在ECOG 0-2和3-4患者中，ORR分别为79.31%（23/29）和75.0%（15/20），PFS分别为15个月（95% CI 5.4-24.6）和4个月（95% CI 0-11.7）。ECOG 0-2患者OS未达到，而ECOG 3-4患者为10.5个月（95% CI 0-22）。单细胞测序表明，治疗疗效可能与mTORC1信号通路相关。
因此，HDS269B疗法对RRMM患者安全有效，即使是ECOG 3-4级患者。
展开英文摘要原文
In this open-label, single-arm, phase I/II clinical trial, we evaluated the efficacy of anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3-4. After HDS269B infusion (9 10 6 CAR + cells/kg), 17 patients (34. 69%, 11 ECOG 0-2, 6 ECOG 3-4) developed cytokine release syndrome [grade 1-2: 14 patients (28. 57%); grade 3: 3 patients (6. 12%)]. The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%.
Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 5. 3-14. 7) and 29 months (95% CI 10. 0-48. 0), respectively. The PFS (12 months) and OS (18 months) rates were 41. 64% and 62. 76%, respectively.
In patients with ECOG 0-2 and 3-4, ORR was 79. 31% (23/29) and 75. 0% (15/20) and PFS were 15 months (95% CI 5. 4-24. 6) and 4 months (95% CI 0-11. 7), respectively. OS was not reached in ECOG 0-2 patients, but was 10. 5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling.
Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4.
论文信息
- 作者
- Du J、Wei R、Jiang S、Jiang H、Li L、Qiang W、He H、Shi L
- 单位
- Department of Hematology, Myeloma & Lymphoma Center, Changzheng Hospital, Naval Medical University, Shanghai, China.China
- 文献类型
- I 期临床试验 · II 期临床试验 · 非美国政府资助研究
- 期刊
- American journal of hematology2022 Jul
- 原文标识
- PubMed 35488407 · DOI 10.1002/ajh.26583