Résumé
7512
Background: In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival (PFS) when compared with observation. RESORT study (Kahl et al. 2014) clearly showed that Rituximab (R) retreatment strategy provided similar time to treatment failure that maintenance strategy with less rituximab use. It is not known whether short MR using sub-cutaneous (sc) route could improve PFS while reducing R infusions. Methods: Patients with the diagnosis of low-tumor burden FL (GELF criteria) within the last 4 months before signing informed consent were randomly assigned to either Iv-Arm : 4-weekly iv infusions of R 375 mg/m
2
or Sc-Arm: one iv infusion of R (D1, 375 mg/m
2
) followed by 3 sc infusions of R (1400 mg, on days 8, 15 and 22) followed by Rsc maintenance on months (M) 3, 5, 7 and 9. The primary endpoint was PFS and secondary endpoints included safety, response rates (M3, M12), duration of response (DOR), time to next anti-lymphoma treatment (TTNTL) and overall survival (OS). Results: A total of 202 patients were included, 102 in Iv-Arm and 100 in Sc-Arm and constitute the intent to treat population. The median uses of R were 4 infusions (range: 1-4, Iv-Arm) and 8 infusions (range: 2-8, Sc-Arm). With a median follow-up of 50.2 months (95% CI: 48.3-54.5), 4‐year PFS was 41.2% (95% CI: 30.6%; 51.6%) in Iv-Arm and 58.1% (95% CI: 47.5%; 67.4%) in Sc-Arm. Median PFS was then 36.1 months (95% IC: 23.9-52.6) in Iv-Arm and 73.8 months (95% CI: 39.4-NA) in Sc-Arm (Fig 1.) (HR: 0.58; 95% CI: 0.39-0.87; P = 0.0076). Patients with at least one AE grade ≥ 3 were 8 (7.8%) and 12 (12.4%) in Iv-Arm and Sc-Arm, respectively. According to Cheson criteria, ORR at M3 were: 83% and 80% including 38% and 29% of CR/CRu, in Iv-Arm and Sc-Arm, respectively. According to Lugano criteria, 36.3% (Iv-Arm; 95% CI: 27.0%. 46.4%) and 59.0% (Sc-Arm; 95% CI: 48.7%; 68.7%) were in CMR at M12. The median DOR was 32.7 months (95% IC: 20.6-49.7) and 70.8 months (36.4-NR) (HR: 0.56; 95% IC: 0.37-0.84) in Iv-Arm and Sc-Arm, respectively. 4-year TTNLT was 54% (95% CI: 42.9%; 63.8%) in Iv-Arm and 61.8% (95% CI: 50.8.6%; 71.0%) in Sc-Arm (HR: 0.81, 95% IC: 0.53-1.24). 4-year TTNLT chemotherapy was 60.8 % (95% CI: 49.6%; 70.3%) in Iv-Arm and 71.4% (95% CI: 60.7%; 79.8%) in Sc-arm (HR: 0.69, 95% IC: 0.42-1.12) (Fig 2.). OS was not different according to treatment arm, 4-year OS was 95.0% (95% CI: 88.5%; 97.9%) in Iv-Arm and 96.7% (95% CI: 89.9%; 98.9%) in Sc-Arm. Conclusions: This phase III study met its primary endpoint and demonstrated that Rsc induction followed by a short MRsc improves PFS of patients with low-tumor burden. MRsc did not however improved TTNLT. R in low-tumor burden FL allowed to avoid cytotoxic use in most patients 6 years after treatment initiation. Clinical trial information: NCT02303119.