As previously reported (Colombat, Blood 2001;97:101), rituximab (4 weekly doses of 375mg/m²) can lead to high response rates (RR) and prolonged remissions with minimal toxicity as 1st line therapy for low tumor burden FL. We report the final analysis of a trial evaluating long term efficacy and safety of rituximab in untreated low tumor burden FL (GELF criteria). 49 patients (pts) were included in the initial trial (median age 52 yrs), 2 refused consent for the extended F/Up period, and 1 pt died at M12. Molecular bcl2-JH rearrangement was assessed throughout the study.
The median F/up was 83.8 mths. Overall best RR, complete/unconfirmed RR and partial RR at D78 were 74%, 50% and 24% respectively. Median PFS was 23.5 mths for the study population. Median duration of response (34 responders at D78, i.e 6 weeks after the last rituximab dose) was 28.6 mths, but response was still maintained without any further treatment in 11 pts after 5 years (24%) and in 7 pts after 7 years (15%).
31/46 pts were bcl2 positive in blood and/or marrow samples before rituximab: 11 (35%) became negative at D50, and 20 remained positive (65%). Median PFS was 37 mths for bcl2-negative pts at D50, and 12 mths for patients remaining positive (p=0.018 Log-rank). Of the 7 pts with sustained response after 7 years, 5 were bcl2 positive at D0, 2/5 became negative at D50, and 5/5 were still negative at M84.
At year 7, 4/46 pts have died (1 from myelodysplasia, 3 from NHL), 35/42 have progressed, and 7 have never progressed without any other treatment than the initial rituximab therapy.
Time to progression was significantly longer in the bcl2-negative population at D50 (p= 0.018, Log-rank). Duration of response was not correlated with bcl2 status at D50, but was associated with ‘Best response CR/Cru’ (p=0.007 Log-rank).
Long-term tolerance was good, with only 13 SAE observed in 13 pts during the additional 4 years of F/Up (4 surgeries for non NHL-related pathologies, 1 node biopsy, 1 sleep apnea syndrome, 1 ischemic cardiopathy, 2 deaths from NHL, 1 depression, 1 pneumonia, 1 erysipela, 1 bronchitis).
This long-term update confirms that a single 4-dose rituximab treatment yields durable benefits without the toxicity of chemotherapy for pts with low burden FL :
1. Median PFS of 23.5 mths for the cohort, 28.6 mths for responders and 37 mths for pts turning bcl2-negative at D50,
2. 15% of pts have maintained their response after 7 years, (2bis) the quality (CR/Cru) of the initial response was associated with a longer response duration
3. high overall survival is observed with 4 deaths/46 pts (8.6%).