Background
Phase III, randomized study. 299 patients with low-tumor-burden FL (GELF criteria not met) who responded to induction rituximab 375mg/m² × 4 weekly doses. Tested rituximab maintenance (single dose every 13 weeks until treatment failure) versus rituximab retreatment (4 weekly doses at time of disease progression). Key question: does ongoing maintenance outperform strategic retreatment at progression?
Interventions and follow up
Arm A: Rituximab maintenance — 375mg/m² IV q13w until treatment failure (progression, toxicity, or completion of protocol)
Arm B: Rituximab retreatment — 375mg/m² IV weekly × 4 doses at each disease progression requiring therapy
Primary endpoint: Time to treatment failure (TTF)
mFollow up: ~7 years (long-term update)
Arm B: Rituximab retreatment — 375mg/m² IV weekly × 4 doses at each disease progression requiring therapy
Primary endpoint: Time to treatment failure (TTF)
mFollow up: ~7 years (long-term update)
Results
Time to chemotherapy (7-year): 83% chemo-free in maintenance arm vs 63% in retreatment arm, HR 2.37, 95% CI 1.50–3.76
10-year OS: 83% (maintenance) vs 84% (retreatment) — identical
Total rituximab doses: Median 18 (maintenance) vs 8 (retreatment) — substantially more rituximab with maintenance
10-year OS: 83% (maintenance) vs 84% (retreatment) — identical
Total rituximab doses: Median 18 (maintenance) vs 8 (retreatment) — substantially more rituximab with maintenance
Adverse events
Hematologic/infectious: Grade ≥3 AEs similar between arms; grade ≥3 infections numerically more frequent in the maintenance arm with longer exposure
Immunologic: Hypogammaglobulinemia more frequent with prolonged maintenance; no significant difference in secondary malignancies
Immunologic: Hypogammaglobulinemia more frequent with prolonged maintenance; no significant difference in secondary malignancies
Conclusions
Rituximab maintenance significantly delayed time to chemotherapy versus retreatment in low-burden FL, but with identical 10-year OS. Maintenance requires substantially more rituximab doses (median 18 vs 8) without OS benefit, raising the question of value in this indolent disease setting.
Key Limitations
The primary TTF endpoint does not account for quality of life or cumulative toxicity of long-term maintenance. Identical OS challenges the clinical value of maintenance despite TTF delay. Substantially more rituximab doses with maintenance increase treatment burden and cost without survival benefit. This trial was conducted before obinutuzumab, PI3K inhibitors, and bispecifics were available — the comparator context has shifted.
Clinical Context
RESORT establishes that in low-tumor-burden FL, retreatment at progression achieves equivalent OS to maintenance, with fewer total treatments — supporting a watch-and-wait or retreatment strategy rather than indefinite maintenance. Major guidelines (ESMO) recommend watchful waiting for asymptomatic low-burden FL, with rituximab-based therapy as an option when treatment is indicated. The Ardeshna trial (Lancet Oncol 2014) separately showed early rituximab vs watch-and-wait delays time to next therapy without OS benefit.
References
Kahl BS et al, JCO 2024 (RESORT long-term follow-up) | Kahl BS et al, JCO 2014 (RESORT primary, PMID: 24799467) | Ardeshna KM et al, Lancet Oncol 2014