实用医学杂志 ›› 2025, Vol. 41 ›› Issue (7): 929-935.doi: 10.3969/j.issn.1006-5725.2025.07.001
• 临床新进展 • 下一篇
收稿日期:
2024-12-10
出版日期:
2025-04-10
发布日期:
2025-04-23
通讯作者:
肖毅
E-mail:yixiao@tjh.tjmu.edu.cn
作者简介:
基金资助:
Received:
2024-12-10
Online:
2025-04-10
Published:
2025-04-23
Contact:
Yi XIAO
E-mail:yixiao@tjh.tjmu.edu.cn
摘要:
多发性骨髓瘤(MM)是一种较常见的血液系统恶性肿瘤,虽然有多种药物可用于其治疗,但仍不可避免复发。近年来B细胞成熟抗原(BCMA)靶向嵌合抗原受体T(CAR-T)细胞治疗在治疗复发/难治性(R/R)MM方面取得了极大的成就,为RRMM患者带来了新的希望。目前国内外已有4种BCMA-CAR-T产品上市,其在RRMM中的应用越来越广泛。但是,BCMA-CAR-T治疗后的RRMM仍有较高的复发率,而对于BCMA-CAR-T后的维持治疗方面的研究仍较少,BCMA-CAR-T治疗复发后的治疗有多种选择。
中图分类号:
燕思佳,肖毅. 多发性骨髓瘤的B细胞成熟抗原靶向嵌合抗原受体T细胞治疗与复发后处理的研究进展[J]. 实用医学杂志, 2025, 41(7): 929-935.
Sijia YAN,Yi XIAO. Advances in BCMA⁃CAR⁃T therapy of multiple myeloma and management after relapse[J]. The Journal of Practical Medicine, 2025, 41(7): 929-935.
1 |
FIRTH J. Haematology: multiple myeloma[J]. Clin Med (Lond),2019,19(1):58-60. doi:10.7861/clinmedicine.19-1-58
doi: 10.7861/clinmedicine.19-1-58 |
2 |
KAZANDJIAN D. Multiple myeloma epidemiology and survival: A unique malignancy[J]. Semin Oncol, 2016,43(6):676-681. doi:10.1053/j.seminoncol.2016.11.004
doi: 10.1053/j.seminoncol.2016.11.004 |
3 |
LEE L, BOUNDS D, HERLEDAN G, et al. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma[J]. Br J Haematol, 2016,174(6):911-922. doi:10.1111/bjh.14145
doi: 10.1111/bjh.14145 |
4 |
POORNIMA S, BINDU K, BINDU G, et al. FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma[J]. Clin Cancer Res, 2022,28(9):1759-1764. doi:10.1158/1078-0432.ccr-21-3803
doi: 10.1158/1078-0432.ccr-21-3803 |
5 |
KAVITA N, MEGHA K, BINDU G, et al. FDA Approval Summary: Ciltacabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma[J]. Clin Cancer Res, 2024,30(14):2865-2871. doi:10.1158/1078-0432.ccr-24-0378
doi: 10.1158/1078-0432.ccr-24-0378 |
6 |
KEAM S J. Equecabtagene Autoleucel: First Approval[J]. Mol Diagn Ther, 2023,27(6):781-787. doi:10.1007/s40291-023-00673-y
doi: 10.1007/s40291-023-00673-y |
7 |
LIN Y, RAJE N S, BERDEJA J G, et al. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: Post hoc 18-month follow-up of a phase 1 trial[J]. Nat Med, 2023,29(9):2286-2294. doi:10.1038/s41591-023-02496-0
doi: 10.1038/s41591-023-02496-0 |
8 |
MUNSHI N C, ANDERSON L D, SHAH N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma[J]. N Engl J Med, 2021,384(8):705-716. doi:10.1056/nejmoa2024850
doi: 10.1056/nejmoa2024850 |
9 |
RODRIGUEZ-OTERO P, AILAWADHI S, ARNULF B, et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma[J]. N Engl J Med, 2023,388(11):1002-1014. doi:10.1056/nejmoa2213614
doi: 10.1056/nejmoa2213614 |
10 |
MARTIN T, USMANI S Z, BERDEJA J G, et al. Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up[J]. J Clin Oncol, 2023,41(6):1265-1274. doi:10.1200/jco.22.00842
doi: 10.1200/jco.22.00842 |
11 |
ZHAO W H, WANG B Y, CHEN L J, et al. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: A phase 1, single-arm, open-label, multicenter study in China (LEGEND-2)[J]. J Hematol Oncol, 2022,15(1):86. doi:10.1186/s13045-022-01301-8
doi: 10.1186/s13045-022-01301-8 |
12 |
MI J Q, ZHAO W, JING H, et al. Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor-T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1)[J]. J Clin Oncol,2023,41(6):1275-1284. doi:10.1200/jco.22.00690
doi: 10.1200/jco.22.00690 |
13 |
VAN DE DONK N W J C, MOUNZER A, ADAM D C, et al. Ciltacabtagene Autoleucel (Cilta-cel), a BCMA-Directed CAR-T Cell Therapy, in Patients with Multiple Myeloma (MM) and Early Relapse after Initial Therapy: CARTITUDE-2 Cohort B 18-Month Follow-up[J]. Blood, 2022,140 (): 7536-7537. doi:10.1182/blood-2022-159169
doi: 10.1182/blood-2022-159169 |
14 |
COHEN A, EINSELE H, DELFORGE M, et al. OAB-045: Updated clinical data and biological correlative analyses of ciltacabtagene autoleucel (cilta-cel) in lenalidomide-refractory multiple myeloma after 1–3 prior lines of therapy: CARTITUDE-2 Cohort A[J]. Clin Lymphoma Myeloma, 2022, 22: S27-S28. doi:10.1016/s2152-2650(22)00318-4
doi: 10.1016/s2152-2650(22)00318-4 |
15 | European Myeloma Network. A Phase 3 Randomized Study Comparing Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible: NCT05257083[R]. clinicaltrials.gov, 2023. |
16 | SAN-MIGUEL J, DHAKAL B, YONG K, et al. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma[J]. N Engl J Med, 2023,389(4):335-347. |
17 |
LI C, WANG D, FANG B, et al. Updated long-term follow-up results of a phase 1b/2 study (FUMANBA-1) in patients with relapsed/refractory multiple myeloma (RRMM) treated with equecabtagene autoleucel[J]. Clin Lymphoma Myeloma, 2023, 23: S196-S197. doi:10.1016/s2152-2650(23)01908-0
doi: 10.1016/s2152-2650(23)01908-0 |
18 |
LI C, WANG D, SONG Y, et al. CT103A, a novel fully human BCMA-targeting CAR-T cells, in patients with relapsed/refractory multiple myeloma: Updated results of phase 1b/2 study (FUMANBA-1)[J]. J Clin Oncol, 2023, 41(): 8025-8025. doi:10.1200/jco.2023.41.16_suppl.8025
doi: 10.1200/jco.2023.41.16_suppl.8025 |
19 |
FU C. Three-Year Follow-up on Efficacy and Safety Results from Phase 1 Lummicar Study 1 of Zevorcabtagene Autoleucel in Chinese Patients with Relapsed or Refractory Multiple Myeloma[J].Blood, 2023, 142(): 4845. doi:10.1182/blood-2023-184373
doi: 10.1182/blood-2023-184373 |
20 |
CHEN W, FU C, FANG B, et al. Phase Ⅱ Study of Fully Human BCMA-Targeting CAR-T Cells (Zevorcabtagene Autoleucel) in Patients with Relapsed/Refractory Multiple Myeloma[J]. Blood, 2022, 140(): 4564-4565. doi:10.1182/blood-2022-168610
doi: 10.1182/blood-2022-168610 |
21 |
WANG Z, ZHOU G, RISU N, et al. Lenalidomide Enhances CAR-T Cell Activity Against Solid Tumor Cells[J]. Cell Transplantation, 2020, 29: 096368972092082. doi:10.1177/0963689720920825
doi: 10.1177/0963689720920825 |
22 |
GARFALL A L, COHEN A D, SUSANIBAR-ADANIYA S P, et al. Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy[J]. Blood Cancer Discov, 2023,4(2):118-133. doi:10.1158/2643-3230.bcd-22-0074
doi: 10.1158/2643-3230.bcd-22-0074 |
23 |
SHI X, YAN L, SHANG J, et al. Anti‐CD19 and anti‐BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem‐cell transplantation for high‐risk newly diagnosed multiple myeloma[J]. Am J Hematol, 2022,97(5):537-547. doi:10.1002/ajh.26486
doi: 10.1002/ajh.26486 |
24 |
ZHOU Z, LIU X, ZHANG X, et al. Effects of Consolidation Therapy With Autologous Hematopoietic Stem Cell Transplantation After BCMA-CAR T-Cell Therapy on the Survival of Patients With Relapsed or Refractory Multiple Myeloma[J].Transplant Cell Ther, 2024,30(11):1080.e1-1080.e11. doi:10.1016/j.jtct.2024.08.024
doi: 10.1016/j.jtct.2024.08.024 |
25 |
LI C. Phase I Clinical Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in the Treatment of Patients With Relapsed/Refractory Extramedullary Multiple Myeloma: NCT05201118[R]. clinicaltrials.gov, 2022. doi:10.1182/blood-2023-181394
doi: 10.1182/blood-2023-181394 |
26 | MOHAN M. A Multicenter Phase Ⅱ Study of Maintenance Belantamab Mafodotin (Blenrep®) After BCMA-Directed Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed and/or Refractory Multiple Myeloma: NCT05117008[R]. clinicaltrials.gov, 2023. |
27 |
FU B, LIU R, GAO G, et al. Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy[J]. Front Immunol, 2024,15:1433774. doi:10.3389/fimmu.2024.1433774
doi: 10.3389/fimmu.2024.1433774 |
28 |
LI W, ZHANG B, CAO W, et al. Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing[J]. Exp Hematol Oncol, 2023,12(1):44. doi:10.1186/s40164-023-00402-5
doi: 10.1186/s40164-023-00402-5 |
29 |
LEDERGOR G, FAN Z, WU K, et al. CD4+ CAR T-cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR T-cell therapy[J]. Blood Adv, 2024,8(13):3562-3575. doi:10.1182/bloodadvances.2023012416
doi: 10.1182/bloodadvances.2023012416 |
30 |
LEE H, AHN S, MAITY R, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma[J]. Nat Med, 2023,29(9):2295-2306. doi:10.1038/s41591-023-02491-5
doi: 10.1038/s41591-023-02491-5 |
31 |
SAMUR M K, FULCINITI M, AKTAS SAMUR A, et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma[J]. Nat Commun,2021,12(1):868. doi:10.1038/s41467-021-21177-5
doi: 10.1038/s41467-021-21177-5 |
32 |
FU B, LIU R, GAO G, et al. Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy[J]. Front Immunol, 2024,15:1433774. doi:10.3389/fimmu.2024.1433774
doi: 10.3389/fimmu.2024.1433774 |
33 |
VAN OEKELEN O, NATH K, MOUHIEDDINE T H, et al. Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy[J]. Blood, 2023,141(7):756-765. doi:10.1182/blood.2022017848
doi: 10.1182/blood.2022017848 |
34 |
CHEN D, WANG X, CHEN Z, et al. Subsequent anti‐myeloma therapy after maturation antigen ( BCMA ) chimeric antigen receptor ( CAR )‐T cell ( HDS269B ) treatment in patients with relapsed/refractory multiple myeloma[J]. Am J Hematol, 2022,97(12):E478-E481. doi:10.1002/ajh.26745
doi: 10.1002/ajh.26745 |
35 |
CHARI A, MINNEMA M C, BERDEJA J G, et al. Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma[J]. N Engl J Med, 2022,387(24):2232-2244. doi:10.1056/nejmoa2204591
doi: 10.1056/nejmoa2204591 |
36 |
TRUDEL S, COHEN A D, KRISHNAN A Y, et al. Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study[J]. Blood, 2021,138 (): 157. doi:10.1182/blood-2021-147983
doi: 10.1182/blood-2021-147983 |
37 |
TOUZEAU C, KRISHNAN A Y, MOREAU P, et al. Efficacy and safety of teclistamab (tec), a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM) after exposure to other BCMA-targeted agents[J]. J Clin Oncol, 2022, 40(): 8013. doi:10.1200/jco.2022.40.16_suppl.8013
doi: 10.1200/jco.2022.40.16_suppl.8013 |
38 |
VAN OEKELEN O, MOUHIEDDINE T H, PAN D, et al. Clinical Outcomes and Treatment Strategies for Relapsed/Refractory Myeloma Patients after Relapse on BCMA-Targeted CAR T[J]. Blood, 2021, 138(): 2704. doi:10.1182/blood-2021-152243
doi: 10.1182/blood-2021-152243 |
39 |
CHARI A, VOGL D T, JAGANNATH S, et al. Selinexor‐based regimens for the treatment of myeloma refractory to chimeric antigen receptor T cell therapy[J]. Br J Haematol, 2020,189(4):e126-e130. doi:10.1111/bjh.16550
doi: 10.1111/bjh.16550 |
40 |
HUANG H. Clinical Trial for the Safety and Efficacy of CS1-targeted CAR-T Cells Therapy for Relapsed Multiple Myeloma After BCMA CAR-T Cells Therapy: NCT04541368[R]. clinicaltrials.gov, 2020. doi:10.31525/ct1-nct04272151
doi: 10.31525/ct1-nct04272151 |
41 |
CHUNG A. Phase II Study of Pembrolizumab in Multiple Myeloma Patients Relapsing After or Refractory to Anti-BCMA CAR-T Therapies: NCT05191472[R]. clinicaltrials.gov, 2022. doi:10.1182/blood-2022-170744
doi: 10.1182/blood-2022-170744 |
42 |
MAILANKODY S, DEVLIN S M, LANDA J, et al. GPRC5D-Targeted CAR T Cells for Myeloma[J]. N Engl J Med, 2022,387(13):1196-1206. doi:10.1056/nejmc2213985
doi: 10.1056/nejmc2213985 |
43 |
XIA J, LI H, YAN Z, et al. Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial[J]. J Clin Oncol, 2023,41(14):2583-2593. doi:10.1200/jco.22.01824
doi: 10.1200/jco.22.01824 |
44 | 石亚群,俞妍慧. 嵌合抗原受体T细胞治疗致细胞因子释放综合征与神经毒性的现状及展望[J]. 实用医学杂志,2021,37(2):268-271. |
[1] | 凤伟祥,王娟,宋艳斌,薛社亮,李文华. 沙库巴曲缬沙坦在行导管消融的非阵发性心房颤动患者中的远期疗效[J]. 实用医学杂志, 2025, 41(7): 1036-1043. |
[2] | 于冰,陈梦霞,王梦迪,黄小榕,张玲娟. 脑卒中患者复发风险感知和健康行为的关系:自我效能和电子健康素养的链式中介作用[J]. 实用医学杂志, 2025, 41(4): 600-606. |
[3] | 崔天玥,欧阳理权,张胜初. 单纯手术与手术联合糖皮质激素治疗肿块型肉芽肿性乳腺炎的临床疗效[J]. 实用医学杂志, 2024, 40(9): 1268-1274. |
[4] | 张碧云,钟兴明,王晓霞,刘晓华. 子宫内膜乳酸杆菌主导的微生物群与生殖的关系[J]. 实用医学杂志, 2024, 40(7): 898-903. |
[5] | 何伟涛,申晓迪,王杨迪,杜金芳,李雪华,熊珊珊,李周雷,林少春. 基于术前磁共振小肠成像预测克罗恩病患者首次肠切除术后早期吻合口复发风险[J]. 实用医学杂志, 2024, 40(5): 664-671. |
[6] | 孔春芳,李安娜,柯波,丁伟荣,刘婷婷,符环,张婷婷,金成豪,吴美. 6-姜辣素对人多发性骨髓瘤细胞的抑制作用及分子机制[J]. 实用医学杂志, 2024, 40(23): 3291-3297. |
[7] | 陈丽萍,罗菊玉,彭章艳,吴秀兰,杨宇宏,石连炎,李笑云,王灵. 肿瘤病灶体积与子宫体积比值和组织中Ki-67、p16蛋白表达与子宫内膜癌病理特征及复发的关联[J]. 实用医学杂志, 2024, 40(23): 3367-3372. |
[8] | 冯娟娟,程泽星,肖路. NLRP3炎性小体水平联合ECP/MPO比值预测慢性鼻窦炎鼻内镜术后复发的临床价值[J]. 实用医学杂志, 2024, 40(22): 3196-3201. |
[9] | 王锐,李多,彭昭,崔利军,张翔,樊凯丽,吴文燕. 经黏膜下隧道内镜肿瘤切除术对贲门周围黏膜下肿瘤患者复发的影响[J]. 实用医学杂志, 2024, 40(18): 2555-2560. |
[10] | 徐思诗,叶佩佩. BTK抑制剂治疗套细胞淋巴瘤的临床研究进展[J]. 实用医学杂志, 2024, 40(17): 2363-2368. |
[11] | 李媛,刘会玲,吴丹,李宝宝. 毒力因子在复发性外阴阴道假丝酵母菌病中的研究进展[J]. 实用医学杂志, 2024, 40(16): 2347-2351. |
[12] | 孙淑玲,邢宇玲,巩建梅,张妮. 三叉神经萎缩和神经脑桥夹角与原发性三叉神经痛患者经皮穿刺射频热凝术后复发的关系[J]. 实用医学杂志, 2024, 40(15): 2133-2137. |
[13] | 念思琦,赵璐露,华宝桐. 心房颤动导管消融术后房性心律失常复发的研究进展[J]. 实用医学杂志, 2024, 40(10): 1338-1343. |
[14] | 戴小颖,沈亚,谭小方. 基于超声子宫内膜容受性参数和淋巴细胞免疫表型对复发性流产再孕早期流产的影响因素分析[J]. 实用医学杂志, 2024, 40(10): 1402-1406. |
[15] | 余江涛 王世杰 张高飞 段鑫鑫 霍青峰 张颂阳 郑守华 刘佩萸 . 血清甲状腺球蛋白、促甲状腺激素联合检测对行甲状腺全切术后未接受清甲治疗的分化型甲状腺癌患者复发的预测价值 [J]. 实用医学杂志, 2023, 39(9): 1159-1163. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||