Subcutaneous vs Intravenous Rituximab in First-Line Treatment of Low–Tumor Burden Follicular Lymphoma

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In a French phase III trial (FLIRT) reported in the Journal of Clinical Oncology, Cartron et al found that the use of subcutaneous (SC) vs intravenous (IV) rituximab was associated with improved progression-free survival in the first-line treatment of low–tumor burden follicular lymphoma.

Study Details

In the multicenter study (a Lymphoma Study Association trial), 202 patients were randomly assigned between February 2015 and June 2018 to receive IV rituximab at 375 mg/m2 once daily on days 1, 8, 15, and 22 (control group, n = 100) or IV rituximab at 375 mg/m2 on day 1 followed by SC rituximab at 1,400 mg total dose once daily on days 8, 15, and 22, with maintenance at 3, 5, 7, and 9 months (experimental group, n = 102). The primary endpoint was progression-free survival.

Key Findings

Progression-free survival at 4 years was 58.1% (95% confidence interval [CI] = 47.5%–67.4%) in the experimental group vs 41.2% (95% CI = 30.6%–51.6%) in the control group (hazard ratio [HR] = 0.585, 95% CI = 0.393–0.871, P = .0076). Complete response rate at 12 months was 59.0% (95% CI = 48.7%–68.7%) in the experimental group vs 36.3% (95% CI = 27.0%–46.4%) in the control group (P = .001). Overall survival rate at 4 years was 96.7% (95% CI =  89.9%–98.9%) in  the experimental group vs 95.0% (95% CI = 88.5%–97.9%) in the control group (P = not significant).

The time to next treatment did not significantly differ between groups. At 4 years, 61.8% (95% CI = 50.8%–71.0%) of the experimental group vs 54.0% (95% CI = 42.9%–63.8%) of the control group had not received next treatment (P = .32).

On multivariate analysis, complete response vs no complete response at month 12 was associated with longer progression-free survival (3-year rate =  75.7% vs 35%, HR =  0.285, P < .001) and time to next treatment (3-year rate = 86.8% vs 33.6%, HR = 0.114, P < .001). On multivariate analysis, high rituximab exposure during the first 3 months was significantly associated with prolonged progression-free survival (HR = 0.428, P = .0010), higher complete response rate (odds ratio = 7.449, P = .016), and prolonged time to next treatment (HR = 0.333, P = .0004).

Prior to month 3, grade ≥ 3 adverse events occurred in seven patients in each group. During maintenance in the experimental group, grade ≥ 3 adverse events occurred in five patients.

Study Implications

The investigators concluded: “SC rituximab improves [progression-free survival] for patients with low–tumor burden [follicular lymphoma] when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes…. [R]ituximab exposure observed within the first 3 months was independently associated with response, [progression-free survival], and [time to next treatment], suggesting that a short rituximab maintenance has a little impact on outcome.”

Guillaume Cartron, MD, PhD, of Centre Hospitalier Universitaire, Montpellier, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was funded by LYSARC (Lymphoma Academic Research Organisation). For full disclosures of all study authors, visit

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