BENDAMUSTINE-RITUXIMAB BETTER THAN R-CHOP FOR INDOLENT LYMPHOMAS 

Lancet. 2013 Feb 19. pii: S0140-6736(12)61763-2. doi: 10.1016/S0140-6736(12)61763-2. [Epub ahead of print]

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial.

Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; on behalf of the Study group indolent Lymphomas (StiL).

Source

Medizinische Klinik IV, Hospital of the Justus-Liebig-University, Giessen, Germany. Electronic address: mathias.rummel@innere.med.uni-giessen.de.

Abstract

BACKGROUND:

Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas.

METHODS:

We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1·4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335.

FINDINGS:

274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69·5 months [26·1 to not yet reached] vs 31·2 months [15·2-65·7]; hazard ratio 0·58, 95% CI 0·44-0·74; p<0 127="" 173="" 23="" 245="" 47="" 73="" alopecia="" and="" bendamustine="" better="" common="" cycles="" erythematous="" group="" haematological="" in="" infections="" lower="" more="" neuropathy="" of="" p="0·024).</p" patients="" peripheral="" plus="" r-chop="" rates="" reactions="" recieved="" rituximab="" skin="" stomatitis="" than="" the="" those="" tolerated="" toxicity="" vs="" was="" were="" who="" with="">

INTERPRETATION:

In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects.