Manteinance Treatment with Interferon (IFN) Is Not Necessary to Achieve Prolonged Progression Free Survival (PFS) in Patients with Indolent Non Hodgkin’s Lymphoma (NHL). Results from a Prospective Randomized Trial on 165 Patients.

INTRODUCTION. Treatment with IFN and chemotherapy induces a significant improvement of PFS in patients with low-grade NHL, specially in patients with responsive disease. However, the best IFN schedule is still pending as benefits are observed when IFN is administered associated to the induction therapy or, as maintenance treatment or, in both treatment phases.

OBJETIVE. To evaluate the additional benefit or not of one year maintenance treatment with IFN in patients who achieve response after an induction treatment with CVP and IFN for 3 months.

PATIENTS & METHODS. From February 1990- October 2002, 165 patients with low-grade NHL were recruited. Patients received treatment with CVP (median number 6 cycles) and IFN, 3MU/m² three times a week during 3 months. Patients with complete or partial responses were then randomized to receive treatment with 12 months of IFN, 3MU/m² three times a week vs observation. With a median of 4,7 years (range 0.3 to 11.7 years) for surviving patients, we analysed response, PFS and overall survival.

RESULTS. Patients median age was 63 years (range 28–89 years), with 65.5% having follicular (FL), 20% small lymphocyte and 14% marginal zone lymphoma. Most patients (83%) were in advance stage and 75% had extranodal involvement. Thirty-three percent of FL patients had a FLIPI index score > 3. Dose-intensity for cyclophosphamide and IFN in the induction treatment was 71% and 69%, respectively. Ten patients withdraw the study due to grade 3–4 toxicity events (6.5%).

Response: 86% of patients achieved a response, 80% complete. One hundred and twelve out of the 143 responding patients were randomised to receive IFN for 12 months (56 patients) vs observation (56 patients). Patients and disease characteristics for each group were similar. Median dose of maintenance IFN treatment was 67% (range 8%–113%). Fourteen patients (25%) withdraw the study, 7 due to IFN toxicity.

PFS: Median PFS of the whole series was 6.76 years, 6.6 years for patients in the maintenance IFN group vs 7.8 years for the observation group, p=0.7.

Overall survival at 12 years is 81% for both groups. Interestingly, 31 patients who achieved a good response but were not randomised showed a significantly shorter OS, p=0.001.

CONCLUSION. No additional increase on PFS has been observed when maintenance IFN is administered to patients responding to CVP and short term IFN induction therapy. With our data, very good response rates and long lasting remission are achieved with only 3 months IFN treatment. Treatment tolerance is therefore significantly better.