Article |
1 Centre hospitalo-universitaire (CHU) de Grenoble, France and
2 INSERM, U 823, Institut Albert Bonniot, Grenoble, France
3 CHU de Rennes
4 CHU de Besançon
5 CHU de Clermont-Ferrand
6 CHU de Tours
7 CHU d'Angers
8 Centre Hospitalier (CH) de Le Mans
9 Institut de cancérologie de la Loire, Saint Etienne
10 CHU Montpellier
11 CHU Nantes
12 CH dAvignon
13 CHU dAmiens
14 clinique Victor Hugo de Le Mans
15 CH La Roche sur Yon
16 CH dAnnecy
17 Centre anticancéreux Baclesse de Caen
18 CHU de Bobigny and
19 Iseres Cancer Registry, Grenoble
Correspondence: Rémy Gressin, Département dOnco-Hématologie, CHU Michallon, BP217, 38043 Grenoble cedex 09 France/Team 7, INSERM-Université Joseph Fourier Research Centre Unité 823, Institut Albert Bonniot, Grenoble, France. Phone: international +33.04.76765333. Fax: international +33.04.76765661. E-mail: RGressin{at}chu-grenoble.fr
ABSTRACT
Background: There is currently no international consensus for first line treatment [prior to autologous stem cells transplantation (auto-SCT)] in mantle cell lymphoma (MCL) patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not [before auto-SCT]
Design and Methods: Between 1996 and 2005, 113 previously untreated MCL-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 [4 courses of (R)VAD+C] showed very low hematologic and extra-hematological toxicity (grade 3–4 thrombopenia and neutropenia, 9% and 2.7% respectively and grade 3–4 extra-haematological toxicities, 1.6%). Overall (ORR) and complete response (CR) rates were 73% and 46%, respectively and raised 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 CR. PFS and OS 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 risks groups with markedly different median OS of 112, 44 and 11 months, respectively.
CONCLUSION: 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 OS.