دورية أكاديمية
17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia.
| العنوان: | 17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia. |
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| المؤلفون: | Bagacean C; U1227 B Lymphocytes and Autoimmunity, University of Brest; INSERM; networks IC-CGO and REpiCGO from 'Canceropole Grand Ouest', Brest, France. cristina.bagacean@univ-brest.fr.; Department of Hematology, Brest University Medical School Hospital, 5 Foch Avenue, BP 824, F-29609, Brest, France. cristina.bagacean@univ-brest.fr.; Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, France. cristina.bagacean@univ-brest.fr., Tempescul A; U1227 B Lymphocytes and Autoimmunity, University of Brest; INSERM; networks IC-CGO and REpiCGO from 'Canceropole Grand Ouest', Brest, France.; Department of Hematology, Brest University Medical School Hospital, 5 Foch Avenue, BP 824, F-29609, Brest, France., Ternant D; University of Tours, EA 7501 Innovation and Cell Targeting Group, CHRU de Tours, Laboratory of Pharmacology-Toxicology, Tours, France., Banet A; Department of Hematology, Brest University Medical School Hospital, 5 Foch Avenue, BP 824, F-29609, Brest, France., Douet-Guilbert N; Laboratory of Cytogenetics, Brest University Medical School Hospital, Brest, France., Bordron A; U1227 B Lymphocytes and Autoimmunity, University of Brest; INSERM; networks IC-CGO and REpiCGO from 'Canceropole Grand Ouest', Brest, France., Bendaoud B; Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, France., Saad H; Department of Hematology, Brest University Medical School Hospital, 5 Foch Avenue, BP 824, F-29609, Brest, France., Zdrenghea M; 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania., Berthou C; U1227 B Lymphocytes and Autoimmunity, University of Brest; INSERM; networks IC-CGO and REpiCGO from 'Canceropole Grand Ouest', Brest, France.; Department of Hematology, Brest University Medical School Hospital, 5 Foch Avenue, BP 824, F-29609, Brest, France., Paintaud G; University of Tours, EA 7501 Innovation and Cell Targeting Group, CHRU de Tours, Laboratory of Pharmacology-Toxicology, Tours, France., Renaudineau Y; Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, France. |
| المصدر: | Journal for immunotherapy of cancer [J Immunother Cancer] 2019 Jan 29; Vol. 7 (1), pp. 22. Date of Electronic Publication: 2019 Jan 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd. Original Publication: London : BioMed Central, 2013- |
| مواضيع طبية MeSH: | Chromosome Deletion* , Chromosomes, Human, Pair 17*, Antineoplastic Agents, Immunological/*pharmacokinetics , Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/*genetics , Rituximab/*pharmacokinetics, Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological/therapeutic use ; Female ; Genetic Variation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Male ; Middle Aged ; Molecular Targeted Therapy ; Neoplasm Staging ; Prognosis ; Rituximab/therapeutic use ; Tumor Suppressor Protein p53/genetics |
| مستخلص: | Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)). This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study. Accordingly, 44 CLL patients were included in the study, and among them 9 presented a del(17p). Next, a total of 233 rituximab sera were selected for a pharmacokinetic study and analyzed in a two-compartment model showing important differences when del(17p) CLL patients were compared with non-del(17p) patients treated with rituximab and chemotherapy: (1) clearance of rituximab was faster; (2) central volume of rituximab distribution V1 (peripheral blood) was reduced while peripheral volume V2 (lymphoid organs and tissues) was increased; and (3) the rate of rituximab elimination (Kout) was faster. In contrast, the group with a better prognosis harboring isolated del(13q) presented a slower rate of elimination (Kout). Pharmacokinetic parameters were independent from the other factors tested such as age, sex, chemotherapy regimen (fludarabine/cyclophosphamide versus bendamustine), IGHV mutational status, and FCGR3A 158VF status. In conclusion, this study provides an additional argument to consider that del(17p) is effective not only to control chemoresistance but also monoclonal antibody activity, based on higher rituximab turnover. |
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| فهرسة مساهمة: | Keywords: 17p deletion; Anti-CD20 monoclonal antibody; Chronic lymphocytic leukemia; Clearance; Pharmacokinetics; Rituximab |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03294980 |
| المشرفين على المادة: | 0 (Antineoplastic Agents, Immunological) 0 (TP53 protein, human) 0 (Tumor Suppressor Protein p53) 4F4X42SYQ6 (Rituximab) |
| تواريخ الأحداث: | Date Created: 20190131 Date Completed: 20200527 Latest Revision: 20200527 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC6352369 |
| DOI: | 10.1186/s40425-019-0509-0 |
| PMID: | 30696487 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2051-1426 |
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| DOI: | 10.1186/s40425-019-0509-0 |