title: Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group.
abstract: Background There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation.
  
  
  METHODS
  Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed.
  
  
  RESULTS
  The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3-4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3-4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389).
authors.affiliation: Département, d'Onco-Hématologie, CHU, Michallon, BP217, 38043 Grenoble cedex 09, France. RGressin@chu-grenoble.fr
authors.forename: Rémy
authors.initials: R
authors.lastname: Gressin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Caulet-Maugendre
authors.forename: Eric
authors.initials: E
authors.lastname: Deconinck
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gyan
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Moles
authors.forename: Abderrazak
authors.initials: A
authors.lastname: El Yamani
authors.forename: Jerome
authors.initials: J
authors.lastname: Cornillon
authors.forename: Jean François
authors.initials: JF
authors.lastname: Rossi
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Gérard
authors.initials: G
authors.lastname: Lepeu
authors.forename: Ghandi
authors.initials: G
authors.lastname: Damaj
authors.forename: Philippe Solal
authors.initials: PS
authors.lastname: Celigny
authors.forename: Hervé
authors.initials: H
authors.lastname: Maisonneuve
authors.forename: Bernadette
authors.initials: B
authors.lastname: Corront
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Vilque
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.forename: Marc
authors.initials: M
authors.lastname: Colonna
authors.forename: Philippe
authors.initials: P
authors.lastname: Colombat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D011446:Prospective Studies; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000379:methods; D013921:Thrombocytopenia / Q000139:chemically induced; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019394:Ki-67 Antigen; D003561:Cytarabine; D002699:Chlorambucil; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone