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Leukemia & Lymphoma

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Adult Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Indolent, Noncontiguous Stage II / III / IV Adult NHL



Rituximab may be considered as first-line therapy, either alone or in combination with other agents.

  • Rituximab alone, as was shown in the ECOG-E4402 (NCT00075946) trial, for example.[23,24,25,26,27]
  • R-Bendamustine: rituximab + bendamustine.[28,29]
  • R-F: rituximab + fludarabine.[30]
  • R-CVP: rituximab + cyclophosphamide + vincristine + prednisone.[31,32]
  • R-CHOP: rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone.[33,34,35] A Cochrane meta-analysis could not identify any OS benefit to adding doxorubicin to chemotherapy regimens with rituximab or to chemotherapy regimens without rituximab.[36][Level of evidence: 1iiA]
  • R-FM: rituximab + fludarabine + mitoxantrone.[37]
  • R-FCM: rituximab + fludarabine + cyclophosphamide + mitoxantrone.[38]

Standard therapy includes rituximab, an anti-CD20 monoclonal antibody, either alone or in combination with purine nucleoside analogs such as fludarabine or 2-chlorodeoxyadenosine, alkylating agents (with or without steroids), or combination chemotherapy.

A prospective, randomized trial of 534 patients with previously untreated, advanced-stage follicular lymphoma compared R-CHOP, R-FM, and R-CVP. With a median follow-up of 34 months, there was no difference in OS, but the 3-year PFS favored R-CHOP (68%) and R-FM (63%) over R-CVP (52%) (P for the three regimens = .011).[39][Level of evidence: 1iiDiii]

Evidence (rituximab):

  • Four randomized, prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis including both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[32,35,40]; [41,42][Level of evidence: 1iiA]
    • Rituximab plus chemotherapy was superior in terms of event-free survival or progression-free survival (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 and hazard ratio [HR] = 0.63 [0.51-0.79] for the meta-analysis).
    • All of these trials were performed in symptomatic patients who required therapy. These results do not negate watchful waiting when appropriate.
    • FDG-PET-CT (fluorine-18-fluorodeoxyglucose-positron-emission tomography-computed tomography) scan status at the completion of rituximab plus chemotherapy induction therapy is strongly predictive of outcome. It is not yet known if acting on the results of the scans translates into better outcomes.[43,44]
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