Rituximab ( MabThera, Rituxan ) 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 ( Levact, Treanda ) plus Rituximab is effective for relapsed or refractory disease.
Researchers have compared Bendamustine plus Rituximab with CHOP plus Rituximab ( R-CHOP ) as first-line treatment for patients with indolent and mantle-cell lymphomas.
Investigators did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 Centres in Germany during the period 2003-2008.
Patients aged 18 years or older with a WHO performance status of two 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/m2 on days 1 and 2 of a 4-week cycle ) or CHOP ( cycles every 3 weeks of Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2, and Vincristine 1.4 mg/m2 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/m2 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.
274 patients were assigned to Bendamustine plus Rituximab ( 261 assessed ) and 275 to R-CHOP ( 253 assessed ).
At median follow-up of 45 months, median progression-free survival was significantly longer in the Bendamustine plus Rituximab group than in the R-CHOP group ( 69.5 months vs 31.2 months; hazard ratio, HR=0.58; p less than 0.0001 ).
Bendamustine plus Rituximab was better tolerated than R-CHOP, with lower rates of alopecia ( 0 patients vs 245 [ 100% ] of 245 patients who recieved greater than or equal to 3 cycles; p less than 0.0001 ), haematological toxicity ( 77 [ 30% ] vs 173 [ 68% ]; p less than 0.0001 ), infections ( 96 [ 37% ] vs 127 [ 50% ] ); p=0.0025 ), peripheral neuropathy ( 18 [ 7% ] vs 73 [ 29% ]; p less than 0.0001 ), and stomatitis ( 16 [ 6% ] vs 47 [ 19% ]; p less than 0.0001 ).
Erythematous skin reactions were more common in patients in the Bendamustine plus Rituximab group than in those in the R-CHOP group ( 42 [ 16% ] vs 23 [ 9% ]; p=0.024 ).
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. ( Xagena )
Rummel MJ et al, The Lancet 2013; 381: 1203-1210