Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).
OBJECTIVE
Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL.


METHODS
One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance.


RESULTS
R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups.


CONCLUSIONS
The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.
Lenz
Georg
G
Department of Internal Medicine III of the Ludwig-Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany.
Dreyling
Martin
M
Hoster
Eva
E
Wörmann
Bernhard
B
Dührsen
Ulrich
U
Metzner
Bernd
B
Eimermacher
Hartmut
H
Neubauer
Andreas
A
Wandt
Hannes
H
Steinhauer
Hjalmar
H
Martin
Sonja
S
Heidemann
Else
E
Aldaoud
Ali
A
Parwaresch
Reza
R
Hasford
Joerg
J
Unterhalt
Michael
M
Hiddemann
Wolfgang
W
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab; D033581:Stem Cell Transplantation; D017211:Treatment Failure; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016898:Interferon-alpha; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone