抗CD38单克隆抗体Isatuximab治疗多发性骨髓瘤的研究进展
Research Progress of Anti-CD38 Monoclonal Antibody Isatuximab in the Treatment of Multiple Myeloma
DOI: 10.12677/ACM.2022.126842, PDF,   
作者: 田闻华：青海大学研究生院，青海 西宁；罗 伟*：青海大学附属医院血液科，青海 西宁
关键词: Isatuximab；CD38；RRMM；NDMM；Isatuximab； CD38； RRMM； NDMM
摘要: 多发性骨髓瘤(MM)是以浆细胞克隆性增殖为特点的血液系统恶性肿瘤，至今仍无法彻底治愈，约占到恶性肿瘤的1%。随着新药的研发与应用，已可以实现MM患者的长期缓解。其中Isatuximab作为新的抗CD38单克隆抗体，在多项对RRMM及NDMM治疗的临床研究中显示了良好的疗效与安全性。本文就Isatuximab单药或联合方案在多发性骨髓瘤的治疗上取得的研究进展作一综述。
Abstract: Multiple myeloma (MM) is a hematological malignancy characterized by plasma cell clonal prolifer-ation, which is still not completely cured, accounting for about 1% of malignant tumors. With the development and application of new drugs, patients with MM can achieve long-term remission. Isatuximab, as a new monoclonal antibody against CD38, has shown good efficacy and safety in a number of clinical studies on RRMM and NDMM. This article reviews the progress of Isatuximab monotherapy or combination in the treatment of multiple myeloma.
文章引用：田闻华, 罗伟. 抗CD38单克隆抗体Isatuximab治疗多发性骨髓瘤的研究进展[J]. 临床医学进展, 2022, 12(6): 5821-5827. https://doi.org/10.12677/ACM.2022.126842

参考文献

[1] Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. [Google Scholar] [CrossRef] [PubMed]
[2] Liu, W., Liu, J., Song, Y., Wang, X., Zhou, M., Wang, L., et al. (2019) Mortality of Lymphoma and Myeloma in China, 2004-2017: An Observational Study. Jour-nal of Hematology & Oncology, 12, Article No. 22. [Google Scholar] [CrossRef] [PubMed]
[3] Kyle, R.A. and Rajkumar, S.V. (2014) Criteria for Diagnosis, Staging, Risk Stratification and Response Assessment of Multiple Myeloma. Leukemia, 28, 980. [Google Scholar] [CrossRef] 
[4] Mohamad, M., Evangelos, T., Maria-Victoria, M., Cavo, M., Lejniece, S., Beksac, M., et al. (2018) Multiple Myeloma Treatment in Real-World Clinical Practice: Results of a Prospective, Multi-national, Noninterventional Study. Clinical Lymphoma, Myeloma & Leukemia, 18, E401-E419. [Google Scholar] [CrossRef] [PubMed]
[5] Malavasi, F., Funaro, A., Roggero, S., Horenstein, A., Calosso, L. and Mehta, K. (1994) Human CD38: A Glycoprotein in Search of a Function. Immunology Today, 15, 95-97. [Google Scholar] [CrossRef] [PubMed]
[6] Martin, T.G., Corzo, K., Chiron, M., van de Velde, H., Abbadessa, G., Campana, F., et al. (2019) Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab. Cells, 8, Article No. 1522. [Google Scholar] [CrossRef] [PubMed]
[7] Krejcik, J., Casneuf, T., Nijhof, I.S., Verbist, B., Bald, J., Plesner, T., et al. (2016) Daratumumab Depletes CD38+ Immune Regulatory Cells, Promotes T-Cell Expansion, and Skews T-Cell Repertoire in Multiple Myeloma. Blood, 128, 384-394. [Google Scholar] [CrossRef] [PubMed]
[8] Aliza-deh, A.A., Eisen, M.B., Davis, R.E., Ma, C., Lossos, I.S., Rosenwald, A., et al. (2000) Distinct Types of Diffuse Large B-Cell Lymphoma Identified by Gene Expressionprofiling. Nature, 403, 503-511. [Google Scholar] [CrossRef] [PubMed]
[9] Brachtl, G., Piñón Hofbauer, J., Greil, R. and Hartmann, T.N. (2013) The Pathogenic Relevance of the Prognostic Markers CD38 and CD49d in Chronic Lymphocytic Leukemia. Annals of He-matology, 93, 361-374. [Google Scholar] [CrossRef] [PubMed]
[10] Keyhani, A., Huh, Y.O., Jendiroba, D., Pagliaro, L., Cortez, J., Pierce, S., et al. (2000) Increased CD38 Expression Is Associated with Favorable Prognosis in Adult Acute Leukemia. Leukemia Research, 24, 153-159. [Google Scholar] [CrossRef] 
[11] Zhu, C., Song, Z., Wang, A., Srinivasan, S., Yang, G., Greco, R., et al. (2020) Isatuximab Acts through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple My-eloma Cells. Frontiers in Immunology, 11, Article No. 1771. [Google Scholar] [CrossRef] [PubMed]
[12] Jiang, H., Acharya, C., An, G., Zhong, M., Feng, X., Wang, L., et al. (2016) SAR650984 Directly Induces Multiple Myeloma Cell Death via Lysosomal-Associated and Apoptotic Path-ways, Which Is Further Enhanced by Pomalidomide. Leukemia, 30, 399-408. [Google Scholar] [CrossRef] [PubMed]
[13] Dhillon, S. (2020) Isatuximab: First Approval. Drugs, 80, 905-912. [Google Scholar] [CrossRef] [PubMed]
[14] Fau, J.B., Cheikh, R.E., Brillac, C., Koiwai, K., Mace, N., Cam-pana, F., et al. (2020) Drug-Disease Interaction and Time-Dependent Population Pharmacokinetics of Isatuximab in Re-lapsed/Refractory Multiple Myeloma Patients. CPT: Pharmacometrics and Systems Pharmacology, 9, 649-658. [Google Scholar] [CrossRef] [PubMed]
[15] Martin, T., Strickland, S., Glenn, M., Charpentier, E., Guillemin, H., Hsu, K., et al. (2019) Phase I Trial of Isatuximab Monotherapy in the Treatment of Refractory Multiple Myeloma. Blood Can-cer Journal, 9, Article No. 41. [Google Scholar] [CrossRef] [PubMed]
[16] Dimopoulos, M.A., Bringhen, S., Anttila, P., Capra, M., Cavo, M., Cole, C.E., et al. (2018) Results from a Phase II Study of Isatuximab as a Single Agent and in Combination with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. Blood, 132, 155. [Google Scholar] [CrossRef] 
[17] Dimopoulos, M., Bringhen, S., Anttila, P., Capra, M., Cavo, M., Cole, C., et al. (2021) Isatuximab as Monotherapy and Combined with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. Blood, 137, 1154-1165. [Google Scholar] [CrossRef] [PubMed]
[18] Bringhen, S., Pour, L., Vorobyev, V., Vural, F., Warzocha, K., Benboubker, L., et al. (2021) Isatuximab plus Pomalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma According to Prior Lines of Treatment and Refractory Status: ICARIA-MM Subgroup Analysis. Leukemia Research, 104, Article ID: 106576. [Google Scholar] [CrossRef] [PubMed]
[19] Richardson, P.G., Perrot, A., San-Miguel, J., Beksac, M., Spicka, I., Schjesvold, F., et al. (2021) MM-130: Updates from ICARIA-MM, a Phase 3 Study of Isatuximab (Isa) Plus Pomalidomide and Low-Dose Dexamethasone (Pd) vs Pd in Relapsed and Refractory Multiple Myeloma (RRMM). Clinical Lymphoma, Myeloma & Leukemia, 21, S423-S424. [Google Scholar] [CrossRef] 
[20] Richardson, P.G., Perrot, A., San-Miguel, J., Beksac, M., Spicka, I., Leleu, X., et al. (2022) Isatuximab plus Pomalidomide and Low-Dose Dexamethasone versus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (ICARIA-MM): Follow-Up Analysis of a Randomised, Phase 3 Study. The Lancet Oncology, 21, 416-427. [Google Scholar] [CrossRef] 
[21] Richardson, P.G., Harrison, S.J., Bringhen, S., Schjesvold, F., Yong, K., Campana, F., et al. (2021) Isatuximab for Relapsed/refractory Multiple Myeloma: Review of Key Subgroup Analyses from the Phase III ICARIA-MM Study. Future oncology, 17, 4797-4812. [Google Scholar] [CrossRef] [PubMed]
[22] Moreau, P., Dimopoulos, M.A., Mikhael, J., Yong, K., Capra, M., Facon, T., et al. (2021) Isatuximab, Carfilzomib, and Dexamethasone in Relapsed Multiple Myeloma (IKEMA): A Mul-ticentre, Open-Label, Randomised Phase 3 Trial. The Lancet, 397, 2361-237. [Google Scholar] [CrossRef] [PubMed]
[23] Martin, T., Mikhael, J., Hajek, R., Kim, K., Suzuki, K., Hulin, C., et al. (2020) Depth of Response and Response Kinetics of Isatuximab plus Carfilzomib and Dexamethasone in Re-lapsed Multiple Myeloma: Ikema Interim Analysis. Blood Advances. [Google Scholar] [CrossRef] 
[24] Capra, M., Martin, T., Moreau, P., Baker, R., Pour, L., Min, C.K., et al. (2021) Isatuximab Plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Relapsed Mul-tiple Myeloma Patients with Renal Impairment: IKEMA Subgroup Analysis. Haematologica, 107, 1397-1409. [Google Scholar] [CrossRef] [PubMed]
[25] Thierry, F., Philippe, M., Thomas, G., Spicka, I., Oriol, A., Koh, Y., et al. (2021) MM-092: Isatuximab Plus Carfilzomib and Dexamethasone versus Carfilzomib and Dexame-thasone in Elderly Patients with Relapsed Multiple Myeloma: IKEMA Subgroup Analysis. Clinical Lymphoma Myeloma and Leukemia, 21, S420. [Google Scholar] [CrossRef] 
[26] Ocio, E.M., Bringhen, S., Oliva, S., Rodriguez-Otero, P., Kanagavel, D., Oprea, C., et al. (2017) A Phase Ib Study of Isatuximab in Combination with Bortezomib, Cyclophos-phamide, and Dexamethasone (VCDI) in Patients with Newly Diagnosed Multiple Myeloma Non-Eligible for Trans-plantation. Blood, 130, 3160.
[27] Ocio, E., Perrot, A., Bories, P., San-Miguel, J.F., Blau, I.W., Karlin, L., et al. (2021) OAB-005: Update of Safety and Efficacy of Isatuximab Short-Duration Fixed-Volume Infusion Plus Bortezomib, Le-nalidomide, and Dexamethasone Combined Therapy for NDMM Ineligible/with No Immediate Intent for ASCT. Clinical Lymphoma Myeloma and Leukemia, 21, S3-S4. [Google Scholar] [CrossRef] 
[28] Ocio, E.M., Perrot, A., Bories, P., San-Miguel, J.F., Blau, I.W., Karlin, L., et al. (2020) Isatuximab Short-Duration Fixed-Volume Infusion Plus Bortezomib (V) Lenalidomide (R) and Dexamethasone(d) Combined Therapy for Newly Diagnosed Multi-ple Myeloma (NDMM): Results from a Phase 1b Feasibility/Safety Study. Blood, 136, 15-16. [Google Scholar] [CrossRef] 
[29] Ocio, E.M., Otero, R., Bringhen, S., Oliva, S., Nogai, A., Attal, M., et al. (2018) Preliminary Results from a Phase I Study of Isatuximab (ISA) in Combination with Bortezomib, Le-nalidomide, Dexamethasone (VRd), and in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Non-Eligible for Transplant. Blood, 132, 595.
[30] Goldschmidt, H., Mai, E.K., Nievergall, E., Fenk, R., Bertsch, U., Tichy, D., et al. (2021) Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone as Induction Therapy for New-ly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial. Blood, 138, Article No. 463. [Google Scholar] [CrossRef] 
[31] Leypoldt, L.B., Besemer, B., Asemissen, A.M., Hänel, M., Blau, I.W., Görner, M., et al. (2021) Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (Isa-KRd) in Front-Line Treatment of High-Risk Multiple Myeloma: Interim Analysis of the GMMG-CONCEPT Trial. Leukemia, 36, 885-888. [Google Scholar] [CrossRef] [PubMed]
[32] Weisel, K., Asemissen, A.M., Besemer, B., Hänel, M., Blau, I.W., Görner, M., et al. (2020) Depth of Response to Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (Isa-KRd) in Front-Line Treatment of High-Risk Multiple Myeloma: Interim Analysis of the GMMG-CONCEPT Trial Journal of Clinical Oncology, 38, 8508. [Google Scholar] [CrossRef] 

为你推荐