title: 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.
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-2within 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.
authors.affiliation: Service de Médecine Interne, CHU Charles Nicolle, Rouen.|Inserm U1096, Rouen, France.|Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.
authors.forename: Ygal
authors.initials: Y
authors.lastname: Benhamou
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, CHRU de Tours, Laboratoire de Pharmacologie-Toxicologie, Tours, France.
authors.forename: Gilles
authors.identifier: 0000-0003-0158-1356
authors.initials: G
authors.lastname: Paintaud
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Hôpital Saint-Louis, AP-HP, Service de Réanimation Médicale, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Hôpital de Marseille Conception, Service d'Hémaphérèse, Marseille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Hôpital Saint-Louis, AP-HP, Service d'Immunologie Clinique, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, CHRU de Tours, Laboratoire de Pharmacologie-Toxicologie, Tours, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Desvignes
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|CHU Saint-Antoine, AP-HP, Service de Réanimation Médicale, Paris, France.|Sorbonne Université, UPMC Univ Paris 06, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Baudel
authors.affiliation: Urgences néphrologiques et transplantation rénale, Hôpital Tenon, AP-HP, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Peltier
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Hôpital Cochin, AP-HP, Service de Réanimation Polyvalente, Paris, France.|Université Paris 5, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Hôpital Cochin, AP-HP, Service de Réanimation Polyvalente, Paris, France.|Université Paris 5, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pène
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Hôpital Sud, Service de Néphrologie-Médecine Interne, Amiens, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Service de Médecine interne 1, Hôpital La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Saheb
authors.affiliation: Service de Médecine interne, CHU de Fort-de France, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Deligny
authors.affiliation: Sorbonne Université, UPMC Univ Paris 06, Paris, France.|Hôpital Saint-Antoine, AP-HP, Unité de Recherche Clinique de l'Est Parisien (URC-Est), Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Sorbonne Université, UPMC Univ Paris 06, Paris, France.|CHU Saint-Antoine, AP-HP, Service d'Immunologie et Hématologie biologique, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Féger
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Hôpital Lariboisière, AP-HP, Service d'Hématologie Biologique, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Centre de Référence des Microangiopathies Thrombotiques, Paris, France.|Inserm U1009, Institut Gustave Roussy, Villejuif, Paris, France.|Hôpital Saint-Antoine, AP-HP, Service d'Hématologie, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
mesh_terms: D000071120:ADAMTS13 Protein / Q000097:blood; D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D065386:Historically Controlled Study; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D010976:Platelet Count; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D000069283:Rituximab / Q000008:administration & dosage*
chemical_list: D000069283:Rituximab; D000071120:ADAMTS13 Protein