title: A phase II Bayesian sequential clinical trial in advanced Waldenström macroglobulinemia patients treated with bortezomib: interest of addition of dexamethasone.
abstract: In patients with advanced Waldenström macroglobulinemia (WM), overall response rate (ORR) and median progression-free survival (PFS) achieved with bortezomib alone and bortezomib rituximab combination were 27-85% and 7.9 months, and 81% and 16.4 months, respectively. We checked the role of dexamethasone in combination with bortezomib by enrolling in a phase II trial 34 patients with relapsed/refractory WM. Bortezomib (1.3 mg/m2IV D1, 4, 8, and 11 every 21 days) was used for six cycles. In non-responding patients, dexamethasone (20 mg daily for two days) was added to each infusion after the second cycle. After two cycles, the Bayes estimated ORR was 43.2 (95% Credible Interval: 28.0-59.1%) using the informative prior. Two-year survival rate was 84.0% and the median PFS 15.3 months without difference between patients treated with or without dexamethasone. We conclude that dexamethasone must be associated to bortezomib-based regimen.
authors.affiliation: a Service d?Hematologie, Hôpital Pitié Salpêtrière APHP GRC-11 UPMC , Paris , France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblond
authors.affiliation: b Service d'Hématologie Clinique , Centre Hospitalier Schaffner , Lens , France.|c Service d'Hématologie Clinique Thérapie Cellulaire , Centre Hospitalier Universitaire Amiens Picardie , Amiens , France.|d Centre d'Etude et de Recherche en Informatique Medicale , Faculté de Médecine pole Recherche , Lille , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.affiliation: e Service d'hématologie et de thérapie cellulaire , Centre François Magendie Hôpital Haut Lévêque , Pessac , France.
authors.forename: Marie-Sarah
authors.initials: MS
authors.lastname: Dilhuidy
authors.affiliation: f Service des maladies du sang , Hopital Huriez CHRU , Lille , France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: g Hôpital René Huguenin-Institut Curie, Service d'Hématologie , Saint-Cloud , France.|h Collège de France, CNRS UMR 7241/INSERM U1050 , Paris , France.
authors.forename: Carole
authors.initials: C
authors.lastname: Soussain
authors.affiliation: i Département d'Hématologie , Centre Henri Becquerel , Rouen , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Leprête
authors.affiliation: j CHU, Service d'Oncologie Hématologie et Thérapie cellulaire , Centre d'investigation clinique Inserm , Poitiers , France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreyfus
authors.affiliation: k Service Hématologie et Thérapie Cellulaire, Pole Henry Kaplan , Hopital Bretonneau , Tours , France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dartigeas
authors.affiliation: l Service d?Hématologie clinique, CHU Hotel Dieu , Nantes , France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mahé
authors.affiliation: m Service d'hématologie , Valence , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Anglaret
authors.affiliation: n Service d?Hématologie Clinique , CHU de Grenoble, Grenoble , France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pégourié
authors.affiliation: o Laboratoire d'hématologie , CHU Bicêtre APHP, Le Kremlin-Bicêtre , France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.affiliation: p Institut Paoli-Calmettes , Marseille , France.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Aurran
authors.affiliation: q Département d'Hématologie Clinique et de Thérapie Cellulaire , Hôpital Saint-Antoine APHP , Paris , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vekhoff
authors.affiliation: r Service d'Hématologie Clinique Adultes de Thérapie Cellulaire , Hôpital Estaing, Université d'Auvergne EA7283, Inserm CIC-501, CHU Clermont-Ferrand , Clermont-Ferrand , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.affiliation: s Service hématologie , Centre hospitalier de la Côte Basque , Bayonne , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Banos
authors.affiliation: t Unité de Recherche Clinique Groupe Hospitalier Pitié-Salpêtrière - Charles Foix APHP , Paris , France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Oya
authors.affiliation: u Service de Biostatistique et Informatique Médicale Hôpital Saint Louis APHP , Paris Cedex , France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lejeune
authors.affiliation: a Service d?Hematologie, Hôpital Pitié Salpêtrière APHP GRC-11 UPMC , Paris , France.
authors.forename: Maya
authors.initials: M
authors.lastname: Ouzegdouh
authors.affiliation: u Service de Biostatistique et Informatique Médicale Hôpital Saint Louis APHP , Paris Cedex , France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001499:Bayes Theorem; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000069286:Bortezomib; D003907:Dexamethasone
keywords: Bayes; Dexamethasone; Waldenström macroglobulinemia; bortezomib