Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia
LI Xiao-Lan, LIU Li-Peng, LIU Fang, GUO Ye, CHEN Xiao-Juan, ZHU Xiao-Fan, YANG Wen-Yu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Institutes of Health Science, Tianjin 300020, China (Yang W-Y, Email: yangwenyu@ihcams.ac.cn)
Abstract：Objective To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL). Methods Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data. Results Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days. Conclusions Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(4): 374-380
LI Xiao-Lan,LIU Li-Peng,LIU Fang et al. Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia[J]. CJCP, 2023, 25(4): 374-380.
Fuster JL, Molinos-Quintana A, Fuentes C, et al. Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP)[J]. Br J Haematol, 2020, 190(5): 764-771. PMID: 32314348. DOI: 10.1111/bjh.16647.
Queudeville M, Schlegel P, Heinz AT, et al. Blinatumomab in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia[J]. Eur J Haematol, 2021, 106(4): 473-483. PMID: 33320384. DOI: 10.1111/ejh.13569.
Sutton R, Pozza LD, Khaw SL, et al. Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomab[J]. Pediatr Blood Cancer, 2021, 68(5): e28922. PMID: 33638292. DOI: 10.1002/pbc.28922.
Beneduce G, De Matteo A, Stellato P, et al. Blinatumomab in children and adolescents with relapsed/refractory B cell precursor acute lymphoblastic leukemia: a real-life multicenter retrospective study in seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) centers[J]. Cancers (Basel), 2022, 14(2): 426. PMID: 35053589. PMCID: PMC8773489. DOI: 10.3390/cancers14020426.
Locatelli F, Maschan A, Boissel N, et al. Pediatric patients with acute lymphoblastic leukemia treated with blinatumomab in a real-world setting: results from the NEUF study[J]. Pediatr Blood Cancer, 2022, 69(4): e29562. PMID: 35044079. DOI: 10.1002/pbc.29562.
von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia[J]. J Clin Oncol, 2016, 34(36): 4381-4389. PMID: 27998223. DOI: 10.1200/JCO.2016.67.3301.
Gore L, Locatelli F, Zugmaier G, et al. Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia[J]. Blood Cancer J, 2018, 8(9): 80. PMID: 30190453. PMCID: PMC6127096. DOI: 10.1038/s41408-018-0117-0.
Locatelli F, Zugmaier G, Mergen N, et al. Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study[J]. Blood Cancer J, 2020, 10(7): 77. PMID: 32709851. PMCID: PMC7381625. DOI: 10.1038/s41408-020-00342-x.
14 U.S. Department Of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE) version 5.0[EB/OL]. [2022-08-25](2017-11-27). https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf
Yang W, Cai J, Shen S, et al. Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial[J]. Lancet Oncol, 2021, 22(9): 1322-1332. PMID: 34329606. PMCID: PMC8416799. DOI: 10.1016/S1470-2045(21)00328-4.
Lejman M, Cha?upnik A, Chilimoniuk Z, et al. Genetic biomarkers and their clinical implications in B-cell acute lymphoblastic leukemia in children[J]. Int J Mol Sci, 2022, 23(5): 2755. PMID: 35269896. PMCID: PMC8911213. DOI: 10.3390/ijms23052755.
Cabannes-Hamy A, Brissot E, Leguay T, et al. High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL[J]. Haematologica, 2022, 107(9): 2072-2080. PMID: 35263986. PMCID: PMC9425331. DOI: 10.3324/haematol.2021.280078.
Aldoss I, Song J, Stiller T, et al. Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia[J]. Am J Hematol, 2017, 92(9): 858-865. PMID: 28494518. DOI: 10.1002/ajh.24783.
Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial[J]. JAMA, 2021, 325(9): 833-842. PMID: 33651090. PMCID: PMC7926290. DOI: 10.1001/jama.2021.0669.
Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody[J]. Science, 2008, 321(5891): 974-977. PMID: 18703743. DOI: 10.1126/science.1158545.
Topp MS, Kufer P, G?kbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival[J]. J Clin Oncol, 2011, 29(18): 2493-2498. PMID: 21576633. DOI: 10.1200/JCO.2010.32.7270.
Hoffmann P, Hofmeister R, Brischwein K, et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct[J]. Int J Cancer, 2005, 115(1): 98-104. PMID: 15688411. DOI: 10.1002/ijc.20908.
Lee YJ, Won TJ, Hyung KE, et al. IL-6 induced proliferation and cytotoxic activity of CD8+ T cells is elevated by SUMO2 overexpression[J]. Arch Pharm Res, 2016, 39(5): 705-712. PMID: 27071615. DOI: 10.1007/s12272-016-0736-6.
Jiang Z, Liao R, Lv J, et al. IL-6 trans-signaling promotes the expansion and anti-tumor activity of CAR T cells[J]. Leukemia, 2021, 35(5): 1380-1391. PMID: 33168950. DOI: 10.1038/s41375-020-01085-1.
