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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



Obinutuzumab is an alternative CD20-binding monoclonal antibody with alternative epitope binding and is being studied in patients with recurrent follicular lymphoma. This agent has shown responses in 20% to 30% of patients when used alone and in 80% of patients when combined with CHOP or FC (fludarabine and cyclophosphamide) in relapsed follicular lymphoma patients.[45,46][Level of evidence: 3iiiDiv]

Purine nucleoside analogs

  • Fludarabine.[1,47,48]
  • 2-chlorodeoxyadenosine.[49,50]

Alkylating agents (with or without steroids)


Evidence (bendamustine):

  1. In a prospective, randomized trial NCT00991211, 527 patients with indolent and mantle cell lymphoma were randomly assigned to a bendamustine-plus-rituximab arm versus an R-CHOP arm.[29][Level of evidence: 1iiDiii]
    • With a median follow-up of 45 months, the median PFS favored the bendamustine arm (69 months vs. 31 months [HR, 0.58; 95 % confidence intervaI (CI), 0.44-0.74; P < .0001]) but with no difference in OS.
    • The bendamustine arm was associated with significantly lower rates of alopecia, hematologic toxicity, stomatitis, peripheral neuropathy, and infections than was the R-CHOP arm.

Combination chemotherapy

  • CVP: cyclophosphamide + vincristine + prednisone.[1,52]
  • CVP followed by rituximab maintenance.[53]
  • C-MOPP: cyclophosphamide + vincristine + procarbazine + prednisone.[54,55]
  • CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.[51,56] 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]
  • FND: fludarabine + mitoxantrone +/- dexamethasone, as evidenced in the SWOG-9501 trial, for example.[57,58]

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.[59,60,61] 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).[62][Level of evidence: 1iiD] Because a significant prolongation of PFS was seen for R-CHOP followed by rituximab maintenance compared with R-CHOP alone,[63] this lack of benefit for CHOP-RIT was particularly disappointing. Iodine-131-labeled tositumomab became commercially unavailable in 2013.

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