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.
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).
Gressin
Rémy
R
Département, d'Onco-Hématologie, CHU, Michallon, BP217, 38043 Grenoble cedex 09, France. RGressin@chu-grenoble.fr
Caulet-Maugendre
Sylvie
S
Deconinck
Eric
E
Tournilhac
Olivier
O
Gyan
Emmanuel
E
Moles
Marie Pierre
MP
El Yamani
Abderrazak
A
Cornillon
Jerome
J
Rossi
Jean François
JF
Le Gouill
Steven
S
Lepeu
Gérard
G
Damaj
Ghandi
G
Celigny
Philippe Solal
PS
Maisonneuve
Hervé
H
Corront
Bernadette
B
Vilque
Jean Pierre
JP
Casassus
Philippe
P
Lamy
Thierry
T
Colonna
Marc
M
Colombat
Philippe
P
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
D058846:Antibodies, Monoclonal, Murine-Derived; D019394:Ki-67 Antigen; D003561:Cytarabine; D002699:Chlorambucil; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone