Adult Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Indolent, Noncontiguous Stage II / III / IV Adult NHL
- 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.
Purine nucleoside analogs
Alkylating agents (with or without steroids)
- CVP: cyclophosphamide + vincristine + prednisone.[1,44]
- CVP followed by rituximab maintenance.
- C-MOPP: cyclophosphamide + vincristine + procarbazine + prednisone.[46,47]
- CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.[43,48]
- FND: fludarabine + mitoxantrone +/- dexamethasone, as evidenced in the SWOG-9501 trial, for example.[49,50]
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, as was shown in the SWOG-9911 trial, for example.[51,52] Randomized prospective studies are required to determine the optimal utilization of this modality.
Evidence (maintenance rituximab):
- In a prospective randomized trial of 465 patients with relapsed follicular lymphoma, responders to R-CHOP or CHOP were further randomly assigned to rituximab maintenance (one dose every 3 months for 2 years) or no maintenance.[Level of evidence: 1iiDiii]
- At 6 years' median follow-up, rituximab maintenance was better for median PFS (44 months vs. 16 months, P < .001) and borderline for 5-year OS (74% vs. 64%, P = .07).
- This benefit for maintenance was evident even for patients who received rituximab during induction therapy. Most patients in both arms received extensive rituximab during post-protocol salvage treatment.
- In the PRIMA study, 1,019 high-risk patients who required treatment achieved complete or partial response after induction therapy with immunochemotherapy (usually R-CHOP) and were then randomly assigned to 2 years of maintenance rituximab versus no maintenance.
- With a median follow-up of 36 months, PFS favored rituximab maintenance 74.9% to 57.6% (HR 0.56, 95% confidence interval 0.44–0.68, P <.0001) but with no difference in OS.
- A meta-analysis of 2,586 patients with follicular lymphoma in nine randomized clinical trials that compared rituximab maintenance with no maintenance showed improved OS for rituximab maintenance in previously treated patients (HR of death, 0.72; 95% CI, 0.57–0.91).[Level of evidence: 1iiA]