Rituximab maintenance improves overall survival of patients with follicular lymphoma-Individual patient data meta-analysis.
Randomised trials of rituximab maintenance (MR) for patients with follicular lymphoma support improved progression-free survival (PFS), but the effect on overall survival has been inconclusive. To evaluate the effect of MR on overall survival according to patient and disease characteristics, and to explore certain adverse events, we performed an individual patient data (IPD) meta-analysis.



All investigators of randomised controlled trials that compared MR therapy with observation or treatment only at relapse (no MR) for patients with follicular lymphoma were invited to participate in an IPD meta-analysis. We obtained baseline patient and disease characteristics and time to progression and death for each patient. All analyses took into account the trial and original randomised treatment group. We analysed data in two ways: a two-stage analysis and a multivariate model including patient and disease characteristics.



Seven trials including 2315 patients were analysed. Overall survival of patients improved with MR compared with no MR (hazard ratio [HR] 0.79, 95% CI 0.66-0.96). We could not detect any patient or disease characteristics that were associated with a survival benefit with MR. In all of the models, MR had a beneficial effect on overall survival compared with observation for all types of patients, which was not shown in a particular subgroup in which the patient had already received rituximab in the induction phase and received first-line therapy. MR improved PFS compared with observation (HR 0.57, 95% CI 0.51-0.64). The risk of adverse events was higher with MR, specifically infection of any grade and grade 3-4 infections.



Based on IPD from randomised controlled trials, MR improves overall survival consistently in all patients, regardless of patient and disease characteristics when compared with observation, and should be prescribed after a successful induction with R-CVP or R-CHOP for patients with follicular lymphoma. It is still uncertain if that holds when the patient has already received rituximab in his/hers first induction. The effect of MR after bendamustine-rituximab induction compared with rituximab at progression should be further explored.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel. Electronic address: vidallit@yahoo.com.
Liat
L
Vidal
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Internal Medicine A, Rabin Medical Center, Petah Tikva, Israel.
Anat
A
Gafter-Gvili
Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Benite, Université Claude Bernard Lyon-1, Lyon, France.
Gilles
G
Salles
Biostatistics Department, LYSARC, Pierre-Benite, France.
Sami
S
Bousseta
Sheba Medical Center, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel.
Bernice
B
Oberman
Sheba Medical Center, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel.
Carmit
C
Rubin
EORTC Lymphoma Group/HOVON, Academic Medical Center, Amsterdam, The Netherlands.
Marinus H J
MH
van Oers
EORTC, Brussels, Belgium.
Catherine
C
Fortpied
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Swiss Group for Clinical Cancer Research, Bern, Switzerland.
Michele
M
Ghielmini
Department of Haematology, St. George's University of London, London, UK.
Ruth
R
Pettengell
Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
Mathias
M
Witzens-Harig
EBMT Lymphoma Working Party, Paris, France.
Peter
P
Dreger
Città della Salute e della Scienza Hospital and University, on behalf of FIL, Turin, Italy.
Umberto
U
Vitolo
CEDOC, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal.
Maria
M
Gomes da Silva
University-Hospital Città della Salute e della Scienza, Torino, Italy.
Andrea
A
Evangelista
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MS, USA.
Hailun
H
Li
Sheba Medical Center, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel.
Laurence
L
Freedman
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Thomas M
TM
Habermann
Assuta Medical Center, Tel Aviv, Israel.
Ofer
O
Shpilberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D060828:Induction Chemotherapy; D007239:Infections / Q000453:epidemiology* / Q000209:etiology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
Follicular lymphoma; Maintenance; Meta-analysis; Rituximab