依鲁替尼在慢性淋巴细胞白血病的临床研究进展
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摘要
依鲁替尼(ibrutinib)是布鲁顿酪氨酸激酶(BTK)抑制剂类的口服靶向抗癌新型药物,能够抑制恶性B淋巴细胞在体内的增殖和存活,主要用于治疗慢性淋巴细胞白血病(CLL),能显著改善患者的总生存期和无进展生存期,实现长期缓解和潜在治愈,开创了治疗CLL的先河。文章就ibrutinib在CLL中的临床研究作一综述。
Ibrutinib is an oral targeted anticancer drug of Bruton's tyrosine kinase(BTK) inhibitors, which can inhibit the proliferation and survival of malignant B lymphocytes in vivo, mainly for the treatment of chronic Lymphocytic leukemia(CLL) can significantly improve the overall survival and progression-free survival of patients, can achieve long-term relief and potential cure, and pioneered the treatment of CLL. This article reviews the clinical study of ibrutinib in CLL.
Ibrutinib is an oral targeted anticancer drug of Bruton's tyrosine kinase(BTK) inhibitors, which can inhibit the proliferation and survival of malignant B lymphocytes in vivo, mainly for the treatment of chronic Lymphocytic leukemia(CLL) can significantly improve the overall survival and progression-free survival of patients, can achieve long-term relief and potential cure, and pioneered the treatment of CLL. This article reviews the clinical study of ibrutinib in CLL.
引文
[1]王志清,徐祖琼,朱学军.新药治疗慢性淋巴细胞白血病的进展[J].临床血液学杂志,2016,29(4):604-608.
[2]Patkar N,Rabade N,Kadam P A,et al.Immunogenetics of chronic lymphocytic leukemia[J].Indian Journal of Pathology&Microbiology,2017,60(1):38-42.
[3]王彦明,钟武,周辛波.口服布鲁顿酪氨酸激酶抑制剂--ibrutinib[J].临床药物治疗杂志,2015,13(4):21-24.
[4]张怀民,傅秀慧,郑海洲.布鲁顿酪氨酸激酶抑制剂ibrutinib治疗恶性肿瘤的作用机制[J].中国医院药学杂志,2018,38(2):209-212.
[5]Itchaki G,Brown J R.Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia[J].Therapeutic Advances in Hematology,2018,9(1):3-19.
[6]Hacken E T,Burger J A.Molecular pathways:targeting the microenvironment in chronic lymphocytic leukemia-focus on the B-cell receptor[J].Clinical Cancer Research,2014,20(3):548-556.
[7]Long M,Beckwith K,Do P,et al.Ibrutinib treatment improves T cell number and function in CLL patients[J].Journal of Clinical Investigation,2017,127(8):3052-3064.
[8]Quinquenel A,Flore S D F,Durot E,et al.Recovery of full donor chimerism with ibrutinib therapy in relapsed CLLafter allogeneic stem cell transplantation[J].British Journal of Haematology,2016,176(6):997-999.
[9]Primo D,Scarfo L,Xochelli A,et al.A novel,ex vivo,highthroughput assay reveals antiproliferative effects of idelalisib and ibrutinib in chronic lymphocytic leukemia[J].Oncotarget,2018,9(40):26019-26031.
[10]Ten Hacken E,Guièze,Romain,Wu C J.SnapShot:Chronic Lymphocytic Leukemia[J].Cancer Cell,2017,32(5):716.
[11]David W,Michael S.Chronic lymphocytic leukemia at ASH2017[J].memo-Magazine of European Medical Oncology,2018,11(2):105-108.
[12]Burger J A,Tedeschi A,Barr P M,et al.Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia-NEJM[J].The New England Journal of Medicine,2011,373(25):2425-2437.
[13]Byrd JC,Brown JR,O’Brien S,et al.Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia[J].The New England Journal of Medicine,2014,371(3):213-223.
[14]Goldwirt L,Beccaria K,Ple A,et al.Ibrutinib brain distribution:a preclinical study[J].Cancer Chemotherapy Pharmacology,2018,81(4):783-789.
[15]Khan K,Malik A I,Almarzouqi S J,et al.Optic Neuropathy Due to Chronic Lymphocytic Leukemia Proven With Optic Nerve Sheath Biopsy[J].Journal of neuro-ophthalmology:the official journal of the North American NeuroOphthalmology Society,2016,36(1):61-66.
[16]Forconi F.Five years of ibrutinib in CLL[J].Blood,2018,131(21):2280-2281.
[17]Fuerst,Mark L.Combination of ibrutinib&venetoclax shows promise in previously treated CLL[J/OL].https://journals.lww.com/oncology-times/blog/onlinefirst/pages/post.aspx?PostID=1770.
[18]Kerry A R,Ying H,Amy S,et al.Phase 1b study of obinutuzumab,ibrutinib,and venetoclax in relapsed and refractory chronic lymphocytic leukemia[J].Blood,2018,132:1568-1572.
[19]Nastoupil L,Lunning M A,Vose J M,et al.Chemo-free triplet combination of TGR-1202,ublituximab,and ibrutinib is well tolerated and highly active in patients with advanced CLLand NHL[J].Hematological,2017,102(S2):312.
[20]Gordon M J,Michael C,Hamood A,et al.Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib[J].Cancer,2018,124(15):3192-3200.
[21]Follows G A,Forum U K C.Outcomes of patients post ibrutinib treatment for relapsed/refractory CLL:A UK and Ireland analysis[J].Hematological Oncology,2017,35(S2):237-238.
[22]Chen T L,Harrington B K,Beaver L,et al.BCL3 overexpression contributes an in vivo growth advantage in a B-cell lymphoma xenograft model and is a risk factor for ibrutinib relapse in CLL[J].Cancer Research,2017,77(S13):3014.
[23]Dreger P,Michallet M,Bosman P,et al.Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma:a study by the EBMT Chronic Malignancies and Lymphoma Working Parties[J].Bone Marrow Transplantation,2018(In Press),doi:10.1038/s41409-018-0207-4.
[24]Ahn IE,Farooqui M Z H,Tian X,et al.Depth and durability of response to ibrutinib in CLL:5-year follow-up of a phase IIstudy.[J].Blood,2018 131:2357-2366.
[25]Sharma S,Galanina N,Guo A,et al.Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL[J].Oncotarget,2016,7(42):68833-68841
[26]Wang,W,Zhou,X,Li,X.Unmask the genetic backbone of ibrutinib-relapsed chronic lymphocytic leukemia progression and Richter transformation[J].Annals of Translational Medicine.2018,6(11):234.
[27]Furman R R,Cheng S,Lu P,et al.Ibrutinib resistance in chronic lymphocytic leukemia[J].New England Journal of Medicine,2014,70(24):2352-2354.
[28]Hamas y A,Wang Q,Blomber g KE,et al.Substitution scanning Identifies a novel,catalytically active ibrutinib-resistant BTK cysteine 481 to threonine(C481T)variant[J].Leukemia,2017,31(1):177-185.
[29]Dasanu CA.Severe arthritic syndrome due to ibrutinib use for chronic lymphocytic leukemia[J].J Oncol Pharm Pract,2018(In Press),doi.org/10.1177/1078155218772327.
[30]Barr PM,Brown JR,Hillmen P,et al.Dose adherence and baseline exposure analysis of the ibrutinib 420 mg dose administered to patients with previously treated CLL.J Clin Oncol 2015;33(S15).abstract 7012.[160]Jain P,Keating M,Wierda W,et al.Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib.Blood2015;125:2062-2067.
[31]Brown J R.How I treat CLL patients with ibrutinib[J].Blood,2018,131(4):379-386.
[32]Anthony R M,Suparna C,Peter P,et al.Left atrial abnormality(LAA)as a predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia[J].Cancer Biology&Therapy,2018,19(1):1-2.
[33]Gianluigi R,Bruno F,Ramona C,et al.Predictors of atrial fibrillation in ibrutinib-treated CLL patients:a prospective study[J].Journal of Hematology&Oncology.2018,11(1):79.
[34]Morrison V A,Rai K R,Peterson B L,et al.Impact of therapy with chlorambucil,fludarabine,or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia:Intergroup study cancer and leukemia group B 9011[J].Journal of Clinical Oncology,2001,19(16):3611-3621.
[35]Kreiniz N,Bejar J,Polliack A,et al.Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma[J].Hematological Oncology,2018,36(1):349-354.
[36]Stein M K,Saradasri K,Jackson R,et al.Cutaneous mucormycosis following a bullous pemphigoid flare in a chronic lymphocytic leukemia patient on ibrutinib[J].World Journal of Oncology,2018,9(2):62-65.
[37]Ensi Voshtina,Huang Huiya,Renju Raj,et al.Amebic encephalitis in a patient with chronic lymphocytic leukemia on ibrutinib therapy[J].Case Reports in Hematology,2018(in press),doi/10.1155/2018/6514604.
[38]Suzuki T,Miyakoshi S,Nanba A,et al.A case of chronic lymphocytic leukemia complicated by autoimmune hemolytic anemia due to ibrutinib treatment[J].Journal of Clinical and Experimental Hematopathology,2018,58(3):136-140.
[39]陈本川.治疗套细胞淋巴瘤及慢性淋巴细胞白血病新药--依鲁替尼(ibrutinib)[J].医药导报,2014,33(10):1336-1338.
[40]Morgan L.Adherence to ibrutinib therapy improves outcomes in patients with CLL[J].Am Health Drug Benefits,2015,8(Spec Issue):39.
[2]Patkar N,Rabade N,Kadam P A,et al.Immunogenetics of chronic lymphocytic leukemia[J].Indian Journal of Pathology&Microbiology,2017,60(1):38-42.
[3]王彦明,钟武,周辛波.口服布鲁顿酪氨酸激酶抑制剂--ibrutinib[J].临床药物治疗杂志,2015,13(4):21-24.
[4]张怀民,傅秀慧,郑海洲.布鲁顿酪氨酸激酶抑制剂ibrutinib治疗恶性肿瘤的作用机制[J].中国医院药学杂志,2018,38(2):209-212.
[5]Itchaki G,Brown J R.Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia[J].Therapeutic Advances in Hematology,2018,9(1):3-19.
[6]Hacken E T,Burger J A.Molecular pathways:targeting the microenvironment in chronic lymphocytic leukemia-focus on the B-cell receptor[J].Clinical Cancer Research,2014,20(3):548-556.
[7]Long M,Beckwith K,Do P,et al.Ibrutinib treatment improves T cell number and function in CLL patients[J].Journal of Clinical Investigation,2017,127(8):3052-3064.
[8]Quinquenel A,Flore S D F,Durot E,et al.Recovery of full donor chimerism with ibrutinib therapy in relapsed CLLafter allogeneic stem cell transplantation[J].British Journal of Haematology,2016,176(6):997-999.
[9]Primo D,Scarfo L,Xochelli A,et al.A novel,ex vivo,highthroughput assay reveals antiproliferative effects of idelalisib and ibrutinib in chronic lymphocytic leukemia[J].Oncotarget,2018,9(40):26019-26031.
[10]Ten Hacken E,Guièze,Romain,Wu C J.SnapShot:Chronic Lymphocytic Leukemia[J].Cancer Cell,2017,32(5):716.
[11]David W,Michael S.Chronic lymphocytic leukemia at ASH2017[J].memo-Magazine of European Medical Oncology,2018,11(2):105-108.
[12]Burger J A,Tedeschi A,Barr P M,et al.Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia-NEJM[J].The New England Journal of Medicine,2011,373(25):2425-2437.
[13]Byrd JC,Brown JR,O’Brien S,et al.Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia[J].The New England Journal of Medicine,2014,371(3):213-223.
[14]Goldwirt L,Beccaria K,Ple A,et al.Ibrutinib brain distribution:a preclinical study[J].Cancer Chemotherapy Pharmacology,2018,81(4):783-789.
[15]Khan K,Malik A I,Almarzouqi S J,et al.Optic Neuropathy Due to Chronic Lymphocytic Leukemia Proven With Optic Nerve Sheath Biopsy[J].Journal of neuro-ophthalmology:the official journal of the North American NeuroOphthalmology Society,2016,36(1):61-66.
[16]Forconi F.Five years of ibrutinib in CLL[J].Blood,2018,131(21):2280-2281.
[17]Fuerst,Mark L.Combination of ibrutinib&venetoclax shows promise in previously treated CLL[J/OL].https://journals.lww.com/oncology-times/blog/onlinefirst/pages/post.aspx?PostID=1770.
[18]Kerry A R,Ying H,Amy S,et al.Phase 1b study of obinutuzumab,ibrutinib,and venetoclax in relapsed and refractory chronic lymphocytic leukemia[J].Blood,2018,132:1568-1572.
[19]Nastoupil L,Lunning M A,Vose J M,et al.Chemo-free triplet combination of TGR-1202,ublituximab,and ibrutinib is well tolerated and highly active in patients with advanced CLLand NHL[J].Hematological,2017,102(S2):312.
[20]Gordon M J,Michael C,Hamood A,et al.Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib[J].Cancer,2018,124(15):3192-3200.
[21]Follows G A,Forum U K C.Outcomes of patients post ibrutinib treatment for relapsed/refractory CLL:A UK and Ireland analysis[J].Hematological Oncology,2017,35(S2):237-238.
[22]Chen T L,Harrington B K,Beaver L,et al.BCL3 overexpression contributes an in vivo growth advantage in a B-cell lymphoma xenograft model and is a risk factor for ibrutinib relapse in CLL[J].Cancer Research,2017,77(S13):3014.
[23]Dreger P,Michallet M,Bosman P,et al.Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma:a study by the EBMT Chronic Malignancies and Lymphoma Working Parties[J].Bone Marrow Transplantation,2018(In Press),doi:10.1038/s41409-018-0207-4.
[24]Ahn IE,Farooqui M Z H,Tian X,et al.Depth and durability of response to ibrutinib in CLL:5-year follow-up of a phase IIstudy.[J].Blood,2018 131:2357-2366.
[25]Sharma S,Galanina N,Guo A,et al.Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL[J].Oncotarget,2016,7(42):68833-68841
[26]Wang,W,Zhou,X,Li,X.Unmask the genetic backbone of ibrutinib-relapsed chronic lymphocytic leukemia progression and Richter transformation[J].Annals of Translational Medicine.2018,6(11):234.
[27]Furman R R,Cheng S,Lu P,et al.Ibrutinib resistance in chronic lymphocytic leukemia[J].New England Journal of Medicine,2014,70(24):2352-2354.
[28]Hamas y A,Wang Q,Blomber g KE,et al.Substitution scanning Identifies a novel,catalytically active ibrutinib-resistant BTK cysteine 481 to threonine(C481T)variant[J].Leukemia,2017,31(1):177-185.
[29]Dasanu CA.Severe arthritic syndrome due to ibrutinib use for chronic lymphocytic leukemia[J].J Oncol Pharm Pract,2018(In Press),doi.org/10.1177/1078155218772327.
[30]Barr PM,Brown JR,Hillmen P,et al.Dose adherence and baseline exposure analysis of the ibrutinib 420 mg dose administered to patients with previously treated CLL.J Clin Oncol 2015;33(S15).abstract 7012.[160]Jain P,Keating M,Wierda W,et al.Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib.Blood2015;125:2062-2067.
[31]Brown J R.How I treat CLL patients with ibrutinib[J].Blood,2018,131(4):379-386.
[32]Anthony R M,Suparna C,Peter P,et al.Left atrial abnormality(LAA)as a predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia[J].Cancer Biology&Therapy,2018,19(1):1-2.
[33]Gianluigi R,Bruno F,Ramona C,et al.Predictors of atrial fibrillation in ibrutinib-treated CLL patients:a prospective study[J].Journal of Hematology&Oncology.2018,11(1):79.
[34]Morrison V A,Rai K R,Peterson B L,et al.Impact of therapy with chlorambucil,fludarabine,or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia:Intergroup study cancer and leukemia group B 9011[J].Journal of Clinical Oncology,2001,19(16):3611-3621.
[35]Kreiniz N,Bejar J,Polliack A,et al.Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma[J].Hematological Oncology,2018,36(1):349-354.
[36]Stein M K,Saradasri K,Jackson R,et al.Cutaneous mucormycosis following a bullous pemphigoid flare in a chronic lymphocytic leukemia patient on ibrutinib[J].World Journal of Oncology,2018,9(2):62-65.
[37]Ensi Voshtina,Huang Huiya,Renju Raj,et al.Amebic encephalitis in a patient with chronic lymphocytic leukemia on ibrutinib therapy[J].Case Reports in Hematology,2018(in press),doi/10.1155/2018/6514604.
[38]Suzuki T,Miyakoshi S,Nanba A,et al.A case of chronic lymphocytic leukemia complicated by autoimmune hemolytic anemia due to ibrutinib treatment[J].Journal of Clinical and Experimental Hematopathology,2018,58(3):136-140.
[39]陈本川.治疗套细胞淋巴瘤及慢性淋巴细胞白血病新药--依鲁替尼(ibrutinib)[J].医药导报,2014,33(10):1336-1338.
[40]Morgan L.Adherence to ibrutinib therapy improves outcomes in patients with CLL[J].Am Health Drug Benefits,2015,8(Spec Issue):39.