Maintenance Rituximab in Advanced Follicular Lymphoma

Maintenance therapy with rituximab showed some improvement over observation, though it did not reach significance, among older patients with advanced follicular lymphoma who responded to a brief chemoimmunotherapy induction regimen followed by rituximab consolidation therapy. The induction and consolidation regimens did produce excellent response rates and progression-free survival (PFS).

Treatment of follicular lymphoma has improved dramatically in recent years, thanks in large part to the use of combination chemoimmunotherapy. Some earlier studies have shown improved PFS with maintenance rituximab following various regimens; the current study, led by Umberto Vitolo, MD, of the Citt della Salute e della Scienza Hospital and University in Torino, Italy, aimed to reduce toxicity with a short induction regimen and rituximab consolidation. The results were published online ahead of print on August 19 in the Journal of Clinical Oncology.

The study included 234 treatment-naive patients with advanced follicular lymphoma; all patients were between the ages of 60 and 75 years. Patients began treatment with 4 monthly courses of rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND); this was followed by 4 weekly cycles of rituximab consolidation therapy. A total of 210 of those patients completed the planned treatment, and 202 responders were randomized to either rituximab maintenance therapy for 8 months (once every 2 months, four total doses) or to an observation group.

After the induction and consolidation regimens, the overall response rate was 86%; 69% of patients experienced a complete remission. After a median follow-up of 42 months from diagnosis, the 3-year PFS rate was 66%, and overall survival was 89%.

After randomization to maintenance or observation, the 2-year PFS was 81% for patients in the rituximab group vs 69% in the observation group; this yielded a non-significant hazard ratio of 0.74 (95% CI, 0.45–1.21; P = .226). There was no difference between the groups with regard to overall survival.

The investigators wrote that the regimen was well tolerated in general, with neutropenia representing the most common grade 3/4 toxicity, occurring in 25% of treatment courses; there were also 13 infections reported, and two toxic deaths (0.8%) occurred during induction treatment.

The authors suggested a few reasons why no significant improvement in PFS was seen with maintenance therapy, as has been demonstrated in earlier studies; these include a short maintenance schedule of only 8 months, as well as a short, 2-year follow-up period.

“However, the lack of significant PFS benefit of this regimen speaks to the lack of universality of maintenance immunotherapy strategies after induction chemoimmunotherapy for this disease,” wrote Caron A. Jacobson, MD, and Arnold S. Freedman, MD, both of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial. The new study, they wrote, shows that less toxic regimens can maintain efficacy in this disease setting, and that the efficacy of maintenance therapy does depend on the induction regimen. “This study does caution against the universal use of rituximab maintenance outside of the contexts in which it has carefully been studied,” they concluded.