Rituximab Maintenance vs Response-Adapted Postinduction Strategy in Advanced Follicular Lymphoma

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In an Italian phase III trial (FOLL12) reported in the Journal of Clinical Oncology, Luminari et al found that a response-adapted postinduction strategy resulted in poorer progression-free survival vs standard rituximab maintenance in patients with previously untreated advanced follicular lymphoma who responded to induction immunochemotherapy.

Study Details

In the open-label multicenter noninferiority trial, 786 eligible patients who responded to induction therapy were randomly assigned between December 2012 and March 2018 to receive 2 years of rituximab maintenance (standard group, n = 393) or treatment based on metabolic response and molecular assessment of measurable residual disease (MRD; experimental group, n = 393). Experimental group treatment consisted of observation in patients with complete metabolic response and MRD-negative status at the end of induction; four doses of rituximab given once per week for a maximum of three courses until achievement of MRD-negative status in those who had complete metabolic response and MRD-positive status; and one dose of ibritumomab tiuxetan followed by standard rituximab maintenance in those who did not have a complete metabolic response. The primary endpoint was progression-free survival, with a noninferiority threshold hazard ratio (HR) of less than 1.309 for the experimental vs standard groups.

Key Findings

The median follow-up was 53 months (range = 1–92 months). Progression-free survival at 3 years was 72% (95% confidence interval [CI] = 67%–76%) in the experimental group vs 86% (95% CI = 82%–89%) in the standard group (HR = 1.92; 95% CI = 1.43–2.56, P < .001).

Improved progression-free survival in the standard group vs experimental group was observed in all study subgroups except for patients who did not have a complete metabolic response. Progression-free survival at 3 years was 90% vs 72% (P < .001) among patients who had a complete metabolic response (n = 628); 50% vs 70% (P = .274) among patients who did not have a complete metabolic response (n = 65); and 92% vs 78% among MRD-negative patients who had a complete metabolic response (n = 299). Among all patients, 3-year progression-free survival was 81% in those with vs 60% in those without complete metabolic response (P < .001).

Overall survival at 3 years was 98% (95% CI = 96%–99%) in the standard group vs 97% (95% CI = 95%–99%) in the experimental group (P = .238).

The investigators concluded: “A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior [progression-free survival] compared with 2-year [rituximab maintenance]. The better efficacy of standard [rituximab maintenance] was confirmed in the subgroup analysis and particularly for patients achieving both [complete metabolic response] and MRD-negative status.”

Stefano Luminari, MD, of the Programma di Ricerca Clinica Oncoematologica, Università di Modena e Reggio Emilia, Reggio Emilia, is the corresponding author of the Journal of Clinical Oncology article.  

Disclosure: The study was supported by the Società Italiana di Ematologia, Associazione Angela Serra per la Ricerca sul Cancro, Ministero della Salute, and others. For full disclosures of the study authors, visit

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