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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.[22,23,24,25,26]
  • R-Bendamustine: rituximab + bendamustine.[27]
  • R-F: rituximab + fludarabine.[28]
  • R-CVP: rituximab + cyclophosphamide + vincristine + prednisone.[29,30]
  • R-CHOP: rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone.[31,32,33]
  • R-FM: rituximab + fludarabine + mitoxantrone.[34]
  • R-FCM: rituximab + fludarabine + cyclophosphamide + mitoxantrone.[35]

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.

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.[30,33,36]; [37,38][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.[39,40]

Purine nucleoside analogs

  • Fludarabine.[1,41,42]
  • 2-chlorodeoxyadenosine.[43,44]

Alkylating agents (with or without steroids)

  • Cyclophosphamide (oral or intravenous).[45]
  • Chlorambucil (oral).

Combination chemotherapy

  • CVP: cyclophosphamide + vincristine + prednisone.[1,46]
  • CVP followed by rituximab maintenance.[47]
  • C-MOPP: cyclophosphamide + vincristine + procarbazine + prednisone.[48,49]
  • CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.[45,50]
  • FND: fludarabine + mitoxantrone +/- dexamethasone, as evidenced in the SWOG-9501 trial, for example.[51,52]

Yttrium-90-labeled ibritumomab tiuxetan and iodine-131-labeled tositumomab

Yttrium-90-labeled ibritumomab tiuxetan and iodine-131-labeled tositumomab are available for previously untreated and relapsing patients with minimal (<25%) or no marrow involvement with lymphoma.[53,54,55] In a randomized, prospective trial, 554 patients with previously untreated advanced-stage follicular lymphoma received either R-CHOP times six cycles or CHOP times six cycles followed by I-131 tositumomab radioimmunotherapy (RIT); with a median follow-up of 4.9 years, there was no significant difference between the PFS and OS (2-year OS, R-CHOP, 97%; CHOP-RIT, 93%; P = .08).[56][Level of evidence: 1iiD] Because a significant prolongation of PFS was seen for R-CHOP followed by rituximab maintenance compared with R-CHOP alone,[57] this lack of benefit for CHOP-RIT was particularly disappointing. A trial compared rituximab-chemotherapy (R-chemotherapy) followed by rituxan maintenance or R-chemotherapy followed by RIT versus R-chemotherapy followed by rituxan maintenance and RIT (SWOG-0801).[58]

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