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Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial
B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injection...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Fondazione Ferrata Storti
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409028/ https://www.ncbi.nlm.nih.gov/pubmed/32817288 http://dx.doi.org/10.3324/haematol.2020.259481 |
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author | Mahévas, Matthieu Azzaoui, Imane Crickx, Etienne Canoui-Poitrine, Florence Gobert, Delphine Languille, Laetitia Limal, Nicolas Guillaud, Constance Croisille, Laure Jeljeli, Mohamed Batteux, Fréderic Baloul, Samia Fain, Olivier Pirenne, France Weill, Jean-Claude Reynaud, Claude-Agnès Godeau, Bertrand Michel, Marc |
author_facet | Mahévas, Matthieu Azzaoui, Imane Crickx, Etienne Canoui-Poitrine, Florence Gobert, Delphine Languille, Laetitia Limal, Nicolas Guillaud, Constance Croisille, Laure Jeljeli, Mohamed Batteux, Fréderic Baloul, Samia Fain, Olivier Pirenne, France Weill, Jean-Claude Reynaud, Claude-Agnès Godeau, Bertrand Michel, Marc |
author_sort | Mahévas, Matthieu |
collection | PubMed |
description | B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at 1 year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single-arm, prospective phase IIb trial investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, 2 weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T-follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety (clinicaltrials gov. Identifier: NCT03154385). |
format | Online Article Text |
id | pubmed-8409028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-84090282021-09-08 Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial Mahévas, Matthieu Azzaoui, Imane Crickx, Etienne Canoui-Poitrine, Florence Gobert, Delphine Languille, Laetitia Limal, Nicolas Guillaud, Constance Croisille, Laure Jeljeli, Mohamed Batteux, Fréderic Baloul, Samia Fain, Olivier Pirenne, France Weill, Jean-Claude Reynaud, Claude-Agnès Godeau, Bertrand Michel, Marc Haematologica Article B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at 1 year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single-arm, prospective phase IIb trial investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, 2 weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T-follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety (clinicaltrials gov. Identifier: NCT03154385). Fondazione Ferrata Storti 2020-08-13 /pmc/articles/PMC8409028/ /pubmed/32817288 http://dx.doi.org/10.3324/haematol.2020.259481 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Mahévas, Matthieu Azzaoui, Imane Crickx, Etienne Canoui-Poitrine, Florence Gobert, Delphine Languille, Laetitia Limal, Nicolas Guillaud, Constance Croisille, Laure Jeljeli, Mohamed Batteux, Fréderic Baloul, Samia Fain, Olivier Pirenne, France Weill, Jean-Claude Reynaud, Claude-Agnès Godeau, Bertrand Michel, Marc Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial |
title | Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial |
title_full | Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial |
title_fullStr | Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial |
title_full_unstemmed | Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial |
title_short | Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial |
title_sort | efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase iib trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409028/ https://www.ncbi.nlm.nih.gov/pubmed/32817288 http://dx.doi.org/10.3324/haematol.2020.259481 |
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