Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis

被引:31
|
作者
Luo, Wenjing [1 ,2 ]
Li, Chenggong [1 ,2 ]
Zhang, Yinqiang [1 ,2 ]
Du, Mengyi [1 ,2 ]
Kou, Haiming [1 ,2 ]
Lu, Cong [1 ,2 ]
Mei, Heng [1 ,2 ]
Hu, Yu [1 ,2 ]
机构
[1] Huazhong Univ Sci & Technol, Inst Hematol, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China
[2] Hubei Clin Med Ctr Cell Therapy Neoplast Dis, Wuhan 430022, Peoples R China
基金
中国国家自然科学基金;
关键词
Chimeric antigen receptor; Hematological malignancies; Hematologic toxicity; Meta-analysis; Review; EFFICACY; SAFETY; REMISSIONS; CHILDREN;
D O I
10.1186/s12885-021-09102-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Recently, chimeric antigen receptor-modified (CAR) T cell therapy for hematological malignancies has shown clinical efficacy. Hundreds of clinical trials have been registered and lots of studies have shown hematologic toxic effects were very common. The main purpose of this review is to systematically analyze hematologic toxicity in hematologic malignancies treated with CAR-T cell therapy. Methods We searched databases including PubMed, Web of Science, Embase and Cochrane up to January 2021. For safety analysis of overall hematologic toxicity, the rate of neutrophil, thrombocytopenia and anemia were calculated. Subgroup analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, history of hematopoietic stem cell transplantation (HSCT) and prior therapy lines. The incidence rate of aspartate transferase (AST) increased, alanine transaminase (ALT) increased, serum creatine increased, APTT prolonged and fibrinogen decreased were also calculated. Results Overall, 52 studies involving 2004 patients were included in this meta-analysis. The incidence of any grade neutropenia, thrombocytopenia and anemia was 80% (95% CI: 68-89%), 61% (95% CI: 49-73%), and 68% (95%CI: 54-80%) respectively. The incidences of grade >= 3 neutropenia, thrombocytopenia and anemia were 60% (95% CI: 49-70%), 33% (95% CI: 27-40%), and 32% (95%CI: 25-40%) respectively. According to subgroup analysis and the corresponding Z test, hematological toxicity was more frequent in younger patients, in patients with >= 4 median lines of prior therapy and in anti-CD19 cases. The subgroup analysis of CD19 CAR-T cell constructs showed that 41BB resulted in less hematological toxicity than CD28. Conclusion CAR-T cell therapy has dramatical efficacy in hematological malignancies, but the relevant adverse effects remain its obstacle. The most common >= 3 grade side effect is hematological toxicity, and some cases die from infections or severe hemorrhage in early period. In long-term follow-up, hematological toxicity is less life-threatening generally and most suffered patients recover to adequate levels after 3 months. To prevent life-threatening infections or bleeding events, clinicians should pay attention to intervention of hematological toxicity in the early process of CAR-T cell therapy.
引用
收藏
页数:20
相关论文
共 50 条
  • [41] Chimeric Antigen Receptor T Cell Therapy for γδ T Cell Malignancies
    Wawrzyniecka, Patrycja A.
    Pule, Martin A.
    Maciocia, Paul M.
    MOLECULAR THERAPY, 2019, 27 (04) : 267 - 268
  • [42] Risk of infectious adverse events of venetoclax therapy for hematologic malignancies: a systematic review and meta-analysis of RCTs
    Prosty, Connor
    Katergi, Khaled
    Nguyen, Alex
    Luo, Owen Dan
    Sorin, Mark
    Cherniak, Vladimir
    Sebag, Michael
    Demir, Koray
    Mcdonald, Emily G.
    Lee, Todd C.
    Cheng, Matthew P.
    BLOOD ADVANCES, 2024, 8 (04) : 857 - 866
  • [43] Cardiovascular effects associated with chimeric antigen receptor T cell therapy in cancer patients: A meta-analysis
    Chen, Li-Rong
    Li, Ya-Jia
    Zhang, Zheng
    Wang, Ping
    Zhou, Tao
    Qian, Kai
    Fan, Yu-Xin
    Guo, Yu
    He, Gong-Hao
    Shen, Lei
    FRONTIERS IN ONCOLOGY, 2022, 12
  • [44] Chimeric Antigen Receptor T-cell Therapy in Hematologic Malignancies and Patient-reported Outcomes: A Scoping Review
    Efficace, Fabio
    Cannella, Laura
    Sparano, Francesco
    Giesinger, Johannes M. M.
    Vignetti, Marco
    Baron, Frederic
    Bruera, Eduardo
    Luppi, Mario
    Platzbecker, Uwe
    HEMASPHERE, 2022, 6 (12): : E802
  • [45] Thirty Day Resource Utilization after Chimeric Antigen Receptor (CAR) T Cell Infusion for Hematologic Malignancies
    Shah, Gunjan L.
    Park, Jae
    Sauter, Craig S.
    Duck, Elaine
    Halton, Elizabeth
    Batlevi, Connie W.
    Palomba, M. Lia
    Younes, Anas
    Geyer, Mark B.
    Smith, Eric
    Mailankody, Sham
    Mead, Elena
    Santomasso, Bianca
    Perales, Miguel-Angel
    Sabbatini, Paul
    Giralt, Sergio A.
    Brentjens, Renier
    Bach, Peter B.
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2019, 25 (03)
  • [46] Chimeric antigen receptor T (CAR-T) cells: Novel cell therapy for hematological malignancies
    Abbasi, Samane
    Totmaj, Milad Asghari
    Abbasi, Masoumeh
    Hajazimian, Saba
    Goleij, Pouya
    Behroozi, Javad
    Shademan, Behrouz
    Isazadeh, Alireza
    Baradaran, Behzad
    CANCER MEDICINE, 2023, 12 (07): : 7844 - 7858
  • [47] Adverse events during chimeric antigen receptor T-cell (CAR-T) therapy for hematologic malignancies (HM): Real-world, US patient experience
    Kish, Jonathan
    Liu, Rachael
    Vennam, Srinivasa
    Lussier, Courtney
    Pfeffer, Daniel
    Nayak, Pratibha
    JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (16)
  • [48] Chimeric Antigen Receptor (CAR) T-cell therapy; a promising outlook for refractory malignancies
    Haider, Syed Ali
    Tariq, Syed Maaz
    Hasan, Mohammad
    JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION, 2018, 68 (09) : 1422 - 1423
  • [49] Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis
    Yu, Min
    Zhang, Qian
    Kong, Fancong
    Qi, Ling
    Pu, Yafang
    Qiu, Lugui
    Wang, Jianxiang
    Li, Fei
    HUMAN GENE THERAPY, 2023, 34 (5-6) : 192 - 202
  • [50] CARDIAC ADVERSE EVENTS ASSOCIATED WITH CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY: A SYSTEMATIC REVIEW
    Thotamgari, Sahith Reddy
    Grewal, Udhayvir
    Shaik, Likhita
    Babbili, Akhilesh
    Dominic, Paari
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2022, 79 (09) : 1901 - 1901