Rituximab alone or in combination with cytotoxic agents used in front-line therapy

R-bendamustine: rituximab + bendamustine.[23-25]

R-F: rituximab + fludarabine.[26]

R-CVP: rituximab + cyclophosphamide + vincristine + prednisone.[27-30]

R-CHOP: rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone.[29-33] A Cochrane meta-analysis could not identify any OS benefit of adding doxorubicin to chemotherapy regimens with rituximab or to chemotherapy regimens without rituximab.[34][Level of evidence A1]

R-FM: rituximab + fludarabine + mitoxantrone.[29,30,35]

R-FCM: rituximab + fludarabine + cyclophosphamide + mitoxantrone.[36]

A prospective randomized trial of 534 patients with previously untreated, advanced-stage, follicular lymphoma compared R-CHOP, R-FM, and R-CVP.[29]

A prospective randomized trial of 534 patients with previously untreated, advanced-stage, follicular lymphoma compared R-CHOP, R-FM, and R-CVP.[29]

With a median follow-up of 84 months, there was no difference in OS (8-year OS rate, 83%; 95% confidence interval [CI], 79%–87%), but the 8-year PFS rates favored R-CHOP (52%) and R-FM (49%) over R-CVP (42%) (P for the three regimens = .037).[29][Level of evidence B1]

Four randomized prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis that included both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[28,33,37]; [38][Level of evidence A1]

Four randomized prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis that included both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[28,33,37]; [38][Level of evidence A1]

Rituximab plus chemotherapy was superior in terms of event-free survival (EFS) or PFS (ranging from 2–3 years) in all of the studies and in terms of OS in all but one study (absolute benefit ranging from 6%–13% at 4 years, P < .04; hazard ratio [HR], 0.63 [0.51–0.79] for the meta-analysis).

Four randomized prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis that included both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[28,33,37]; [38][Level of evidence A1]

All of these trials were performed in symptomatic patients who required therapy. These results do not negate watchful waiting when appropriate.

Four randomized prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis that included both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[28,33,37]; [38][Level of evidence A1]

Fluorine F 18-fludeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) scan status at the completion of rituximab plus chemotherapy induction therapy is strongly predictive of outcome. It is not yet known whether acting on the results of the scans translates into better outcomes.[39,40]

In a prospective randomized trial (NCT00991211), 527 patients with indolent and mantle cell lymphoma were randomly assigned to receive either bendamustine and rituximab or R-CHOP.[24][Level of evidence B1]

In a prospective randomized trial (NCT00991211), 527 patients with indolent and mantle cell lymphoma were randomly assigned to receive either bendamustine and rituximab or R-CHOP.[24][Level of evidence B1]

With a median follow-up of 45 months, the median PFS favored the bendamustine arm (69 months vs. 31 months [HR, 0.58; 95% CI, 0.44–0.74; P < .0001]) but with no difference in OS.

In a prospective randomized trial (NCT00991211), 527 patients with indolent and mantle cell lymphoma were randomly assigned to receive either bendamustine and rituximab or R-CHOP.[24][Level of evidence B1]

Compared with the R-CHOP arm, the bendamustine arm was associated with significantly lower rates of alopecia, hematologic toxicity, stomatitis, peripheral neuropathy, and infections.

In a similar prospective randomized trial, 447 patients with indolent and mantle cell lymphoma were assigned to bendamustine and rituximab versus R-CHOP or R-CVP.[25][Level of evidence B1]

In a similar prospective randomized trial, 447 patients with indolent and mantle cell lymphoma were assigned to bendamustine and rituximab versus R-CHOP or R-CVP.[25][Level of evidence B1]

With a median follow-up of 65 months, the 5-year PFS rate favored bendamustine and rituximab, 65.5% versus 55.8% (HR, 0.61; 95% CI, 0.45–0.85; P = .0025), but with no difference in OS.

In a similar prospective randomized trial, 447 patients with indolent and mantle cell lymphoma were assigned to bendamustine and rituximab versus R-CHOP or R-CVP.[25][Level of evidence B1]

Increased deaths in the bendamustine-and-rituximab arm from cardiovascular causes (seven vs. one) and from secondary malignancies other than lymphoma (five vs. three) may have contributed to the lack of OS advantage.