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Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II,multicenter noncomparative study |
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| Authors: | Ygal Benhamou Gilles Paintaud Elie Azoulay Pascale Poullin Lionel Galicier Céline Desvignes Jean‐Luc Baudel Julie Peltier Jean‐Paul Mira Frédéric Pène Claire Presne Samir Saheb Christophe Deligny Alexandra Rousseau Frédéric Féger Agnès Veyradier Paul Coppo French Reference Center for Thrombotic Microangiopathies |
| Institution: | 1. Service de Médecine Interne, CHU Charles Nicolle, Rouen;2. Inserm U1096, Rouen, France;3. H?pital Saint‐Antoine, AP‐HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France;4. Université Fran?ois‐Rabelais de Tours, CNRS, GICC UMR 7292, CHRU de Tours, Laboratoire de Pharmacologie‐Toxicologie, Tours, France;5. H?pital Saint‐Louis, AP‐HP, Service de Réanimation Médicale, Paris, France;6. Université Paris Diderot, Sorbonne Paris Cité, Paris, France;7. H?pital de Marseille Conception, Service d'Hémaphérèse, Marseille, France;8. H?pital Saint‐Louis, AP‐HP, Service d'Immunologie Clinique, Paris, France;9. CHU Saint‐Antoine, AP‐HP, Service de Réanimation Médicale, Paris, France;10. Sorbonne Université, UPMC Univ Paris 06, Paris, France;11. Urgences néphrologiques et transplantation rénale, H?pital Tenon, AP‐HP, Paris, France;12. H?pital Cochin, AP‐HP, Service de Réanimation Polyvalente, Paris, France;13. Université Paris 5, Paris, France;14. H?pital Sud, Service de Néphrologie—Médecine Interne, Amiens, France;15. Service de Médecine interne 1, H?pital La Pitié‐Salpêtrière, AP‐HP, Paris, France;16. Service de Médecine interne, CHU de Fort‐de France, France;17. H?pital Saint‐Antoine, AP‐HP, Unité de Recherche Clinique de l'Est Parisien (URC‐Est), Paris, France;18. CHU Saint‐Antoine, AP‐HP, Service d'Immunologie et Hématologie biologique, Paris, France;19. H?pital Lariboisière, AP‐HP, Service d'Hématologie Biologique, Paris, France;20. Inserm U1009, Institut Gustave Roussy, Villejuif, Paris, France;21. H?pital Saint‐Antoine, AP‐HP, Service d'Hématologie, Paris, France |
| Abstract: | The standard four‐rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti‐ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange‐based regimen received two infusions of rituximab 375 mg m?2 within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell‐driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti‐ADAMTS13 depletion in a similar manner to the standard four‐rituximab infusions schedule. The 1‐year relapse‐free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four‐rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246–1251, 2016. © 2016 Wiley Periodicals, Inc. |
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