Treatment for Indolent, Noncontiguous Stage II / III / IV Adult NHL
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]
Many questions remain about rituximab maintenance, particularly about truncating therapy at 2 years and long-term safety and efficacy. The most salient question is whether a strategy of observation after induction with rituximab therapy at time of symptomatic progression is equivalent or superior to mandated rituximab maintenance.
Treatment Options Under Clinical Evaluation for Indolent, Noncontiguous Stage II/III/IV Adult NHL
Since none of the standard therapies listed above are curative for advanced-stage disease, innovative approaches are under clinical evaluation. The approaches include intensive therapy with chemotherapy and total-body irradiation (TBI) followed by autologous or allogeneic bone marrow transplantation (BMT) or peripheral stem cell transplantation, and the use of idiotype vaccines and radiolabeled monoclonal antibodies.
- Intensive therapy with chemotherapy with or without TBI or high-dose radioimmunotherapy followed by autologous or allogeneic BMT or peripheral stem cell transplantation is under clinical evaluation.[58,59,60,61,62,63,64,65,66]
- Phase III trials comparing chemotherapy alone versus chemotherapy followed by anti-idiotype vaccine.[67,68,69]
- Extended-field radiation therapy (stage III patients only).
- Ofatumumab—human anti-CD20 monoclonal antibody.
- Short-course low-dose, palliative radiation therapy (2 × 2 Gy).[72,73]