Maintenance interferon-alpha (IFNa) immunotherapy after induction chemotherapy prolongs progression-free survival (PFS) in untreated follicular lymphoma (FL). Little information is available about IFNa use in relapsed FL.


To evaluate the benefit of IFNa as treatment for low-burden FL relapse.


In this single-centre retrospective study, we analysed all patients with molecular or clinical relapsed low- burden FL who received 3MIU IFNa three times a week alone (16 times) or in combination with 4-weekly rituximab (R) (11 times), without chemotherapy, according to the institution’s policy. All responses were evaluated according to the IWG 1999 criteria, except for molecular relapses which are described separately.


20 patients (13 men, 7 women), treated for a total of 27 times with IFNa were identified, with a median follow-up of 85 months. At diagnosis, 17 patients had advanced III-IV stage and 5 of them a high tumour burden, according to GELA criteria. 5 patients were treated for molecular IGH-BCL2 relapses. The FLIPI score was intermediate or high risk in 37% of patients. The median age of patients at the first IFNa +/- R treatment was 51 years (range: 30-65). Patients had previously received a median of three lines of treatment (range: 1-6) and 59% had received anthracycline-based chemotherapy. In the 22 situations with measurable disease, the overall response rate (OR) was 70%, with 59% complete responses (CR). For patients with only detectable molecular disease (n=5), IFNa was used alone for a median duration of 15 months (range: 12- 21 months), MRD becoming negative in 4 patients. The only factor significantly correlated with maximum response was low FLIPI score calculated at study entry (p=0.02). Median PFS was 56.9 months, (95% CI: 0.8-113). The R-IFNa and IFNa subgroup outcomes did not statistically differ in response or PFS. The FLIPI score calculated at initiation of IFNa treatment was predictive of time to relapse (P=0.014). The overall survival at 5 years was 95 % (95%CI: 91-99): 100%  in the  IFNa group and 91% (95%CI: 82-100) in the R-IFNa group. Reported toxicity was low.


Interferon alpha with or without rituximab achieve high response rates in relapsed low burden follicular lymphoma. These results compare favorably with previous reports of the efficacy of R alone, and of R with IFNa in relapse. Further research is required to explore the role of IFNa in the management of FL.


Gyan:Roche: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.

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