博纳吐单抗治疗急性B淋巴细胞白血病的疗效和安全性

摘要/Abstract

摘要：

博纳吐单抗作为靶向CD19和CD3的新型双特异性抗体,可诱导T淋巴细胞精准靶向CD19阳性B淋巴细胞使其凋亡,是目前国内唯一被批准用于治疗血液恶性肿瘤的双特异性抗体,对初诊断、复发/难治性、微小残留病阳性的急性B淋巴细胞白血病（B-ALL）患者有较好的疗效,可改善患者生存期,且耐受性良好。对其深入研究可为博纳吐单抗用于B-ALL患者的诱导治疗、挽救治疗和序贯造血干细胞移植提供理论依据和新的思路。

关键词:博纳吐单抗,双特异性抗体,急性B淋巴细胞白血病,疗效,安全性

Abstract:

Blinatumomab, as a novel bispecific antibody targeting CD19 and CD3, can induce T lymphocytes to precisely target CD19 positive B lymphocytes to apoptosis. At present, it is the only bispecific antibody approved for the treatment of hematological malignancies in China. Blinatumomab is effective in the treatment of newly diagnosed, relapsed/refractory, minimal residual disease positive patients with B-cell acute lymphoblastic leukemia （B-ALL）. It can improve the survival of the patients and is well tolerated. The further study of blinatumomab can provide theoretical basis and new ideas for induction therapy, salvage therapy and subsequent hematopoietic stem cell transplantation in patients with B-ALL.

Key words:Blinatumomab,Bispecific antibody,B-cell acute lymphoblastic leukemia,Efficacy,Safety

陆佳玲, 黄慧娟, 刘丹, 陈妍心, 马骁, 吴德沛. 博纳吐单抗治疗急性B淋巴细胞白血病的疗效和安全性[J]. 国际肿瘤学杂志, 2022, 49(8): 494-498.

Lu Jialing, Huang Huijuan, Liu Dan, Chen Yanxin, Ma Xiao, Wu Depei. Efficacy and safety of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia[J]. Journal of International Oncology, 2022, 49(8): 494-498.

参考文献27

[1]	Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia[J]. Blood, 2018, 131(14): 1522-1531. DOI: 10.1182/blood-2017-08-798322. doi:10.1182/blood-2017-08-798322pmid:29358182
[2]	Jabbour E, O'Brien S, Konopleva M, et al. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia[J]. Cancer, 2015, 121(15): 2517-2528. DOI: 10.1002/cncr.29383. doi:10.1002/cncr.29383pmid:25891003
[3]	Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia[J]. N Engl J Med, 2017, 376(9): 836-847. DOI: 10.1056/NEJMoa1609783. doi:10.1056/NEJMoa1609783
[4]	Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study[J]. Lancet Oncol, 2015, 16(1): 57-66. DOI: 10.1016/S1470-2045(14)71170-2. doi:10.1016/S1470-2045(14)71170-2pmid:25524800
[5]	Dombret H, Topp MS, Schuh AC, et al. Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia[J]. Leuk Lymphoma, 2019, 60(9): 2214-2222. DOI: 10.1080/10428194.2019.1576872. doi:10.1080/10428194.2019.1576872
[6]	Martinelli G, Boissel N, Chevallier P, et al. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: final analysis of ALCANTARA study[J]. Eur J Cancer, 2021, 146: 107-114. DOI: 10.1016/j.ejca.2020.12.022. doi:10.1016/j.ejca.2020.12.022pmid:33588145
[7]	Sasaki K, Kantarjian HM, Ravandi F, et al. Sequential combination of low-intensity chemotherapy (mini-hyper-CVD) plus inotuzumab ozogamicin with or without blinatumomab in patients with relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL): a phase 2 trial[J]. Blood, 2018, 132(Supplement 1): 553. DOI: 10.1182/blood-2018-99-115162. doi:10.1182/blood-2018-99-115162
[8]	Badar T, Szabo A, Dinner S, et al. Sequencing of novel agents in relapsed/refractory B-cell acute lymphoblastic leukemia: blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia[J]. Cancer, 2021, 127(7): 1039-1048. DOI: 10.1002/cncr.33340. doi:10.1002/cncr.33340
[9]	Assi R, Kantarjian H, Short NJ, et al. Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome-positive leukemia[J]. Clin Lymphoma Myeloma Leuk, 2017, 17(12): 897-901. DOI: 10.1016/j.clml.2017.08.101. doi:10.1016/j.clml.2017.08.101
[10]	von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase Ⅰ/phaseⅡ study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia[J]. J Clin Oncol, 2016, 34(36): 4381-4389. DOI: 10.1200/JCO.2016.67.3301. doi:10.1200/JCO.2016.67.3301pmid:27998223
[11]	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. DOI: 10.1001/jama.2021.0669. doi:10.1001/jama.2021.0669
[12]	Clesham K, Rao V, Bartram J, et al. Blinatumomab for infant acute lymphoblastic leukemia[J]. Blood, 2020, 135(17): 1501-1504. DOI: 10.1182/blood.2019004008. doi:10.1182/blood.2019004008
[13]	Contreras CF, Higham CS, Behnert A, et al. Clinical utilization of blinatumomab and inotuzumab immunotherapy in children with relapsed or refractory B-acute lymphoblastic leukemia[J]. Pediatr Blood Cancer, 2021, 68(1): e28718. DOI: 10.1002/pbc.28718. doi:10.1002/pbc.28718
[14]	Brethon B, Lainey E, Caye-Eude A, et al. Case report: targeting 2 antigens as a promising strategy in mixed phenotype acute leukemia: combination of blinatumomab with gemtuzumab ozogamicin in an infant with a KMT2A-rearranged leukemia[J]. Front Oncol, 2021, 11: 637951. DOI: 10.3389/fonc.2021.637951. doi:10.3389/fonc.2021.637951
[15]	Choi HJ, Choi JY, Kim BK, et al. Combination therapy with chemotherapy, donor lymphocyte infusion with concurrent blinatumomab in relapsed/refractory acute precursor B-lymphoblastic leukemia[J]. J Pediatr Hematol Oncol, 2021, 43(2): e280-e283. DOI: 10.1097/MPH.0000000000001789. doi:10.1097/MPH.0000000000001789
[16]	Gökbuget N, Zugmaier G, Dombret H, et al. Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia[J]. Leuk Lymphoma, 2020, 61(11): 2665-2673. DOI: 10.1080/10428194.2020.1780583. doi:10.1080/10428194.2020.1780583
[17]	Efficacy and safety of the BiTE antibody blinatumomab in Chinese adult subjects with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL)[DB/OL]. [2020-09-14][2022-05-02]. https://clinicaltrials.gov/ct2/show/NCT03476239?term=NCT03476239&draw=2&rank=1.
[18]	Aldoss I, Yang D, Malki MMA, et al. Allogeneic hematopoietic cell transplantation for relapsed and refractory Philadelphia negative B cell ALL in the era of novel salvage therapies[J]. Transplant Cell Ther, 2021, 27(3): 255.e1-255.e9. DOI: 10.1016/j.jtct.2020.12.020. doi:10.1016/j.jtct.2020.12.020
[19]	Advani AS, Moseley A, O'Dwyer KM, et al. Results of SWOG 1318: a phase 2 trial of blinatumomab followed by pomp (prednisone, vincristine, methotrexate, 6-mercaptopurine) maintenance in elderly patients with newly diagnosed Philadelphia chromosome negative B-cell acute lymphoblastic leukemia[J]. Blood, 2018, 132(Supplement 1): 33. DOI: 10.1182/blood-2018-99-111992. doi:10.1182/blood-2018-99-111992
[20]	Richard-Carpentier G, Kantarjian HM, Short NJ, et al. Updated results from the phase Ⅱ study of hyper-CVAD in sequential combination with blinatumomab in newly diagnosed adults with B-cell acute lymphoblastic leukemia (B-ALL)[J]. Blood, 2019, 134(Supplement 1): 3807. DOI: 10.1182/blood-2019-129657. doi:10.1182/blood-2019-129657
[21]	Foà R, Bassan R, Vitale A, et al. Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults[J]. N Engl J Med, 2020, 383(17): 1613-1623. DOI: 10.1056/NEJMoa2016272. doi:10.1056/NEJMoa2016272
[22]	Schober S, Cabanillas Stanchi KM, Riecker A, et al. Fulminant Rhizomucor pusillus mucormycosis during anti-leukemic treatment with blinatumomab in a child: a case report and review of the literature[J]. Med Mycol Case Rep, 2020, 32: 4-9. DOI: 10.1016/j.mmcr.2020.12.002. doi:10.1016/j.mmcr.2020.12.002
[23]	Elitzur S, Arad-Cohen N, Barzilai-Birenboim S, et al. Blinatumomab as a bridge to further therapy in cases of overwhelming to-xicity in pediatric B-cell precursor acute lymphoblastic leukemia: report from the Israeli Study Group of Childhood Leukemia[J]. Pediatr Blood Cancer, 2019, 66(10): e27898. DOI: 10.1002/pbc.27898. doi:10.1002/pbc.27898
[24]	Mejstríková E, Hrusak O, Borowitz MJ, et al. CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment[J]. Blood Cancer J, 2017, 7(12): 659. DOI: 10.1038/s41408-017-0023-x. doi:10.1038/s41408-017-0023-xpmid:29259173
[25]	Zoghbi A, Zur Stadt U, Winkler B, et al. Lineage switch under blinatumomab treatment of relapsed common acute lymphoblastic leukemia without MLL rearrangement[J]. Pediatr Blood Cancer, 2017, 64(11): 26594. DOI: 10.1002/pbc.26594. doi:10.1002/pbc.26594
[26]	Du J, Chisholm KM, Tsuchiya K, et al. Lineage switch in an infant B-lymphoblastic leukemia with t(1;11)(p32;q23); KMT2A/EPS15, following blinatumomab therapy[J]. Pediatr Dev Pathol, 2021, 24(4): 378-382. DOI: 10.1177/10935266211001308. doi:10.1177/10935266211001308
[27]	Zhao Y, Aldoss I, Qu C, et al. Tumor-intrinsic and -extrinsic determinants of response to blinatumomab in adults with B-ALL[J]. Blood, 2021, 137(4): 471-484. DOI: 10.1182/blood.2020006287. doi:10.1182/blood.2020006287