The Italian Experience on Interferon as Maintenance Treatment in Multiple Myeloma: Ten Years After

To the Editor:

The role of interferon maintenance treatment in patients with multiple myeloma (MM) is still debated. In 1990, the Italian Multiple Myeloma Study Group published the results of the first randomized study on the role of interferon a2-b (IFN) as maintenance treatment in patients responding to induction therapy.1 One hundred one MM patients responding to traditional first-line induction chemotherapy were randomized to receive (n = 50) or not receive (n = 51) IFN maintenance. Patients were recruited from a group of 202 symptomatic MM patients observed in the three university institutions of Rome, Bari, and Turin, Italy. The results originally demonstrated that a maintenance treatment with IFN prolonged response and survival duration in patients with MM who have responded to conventional induction therapy.

After this experience, five large randomized studies were published comparing IFN maintenance versus untreated control: two of them did not demonstrate any advantage as for response and survival duration^2,3; one showed a clear advantage in response duration but not in survival duration⁴; and two demonstrated a significant improvement both in response duration and in survival duration.5,6 

The updated results of the Italian study 9 years after the randomization of the last patient confirm a significant prolongation of response duration in IFN maintained patients: the median response duration (from time of randomization to maintenance treatment) is 24 months in patients receiving IFN and 13 months in untreated patients (P = .0016). The results in terms of prolongation of survival are less significant: the median overall survival is of 50 and 39 months, respectively (P = .21); among patients who had an objective response to induction chemotherapy (>50% reduction in M protein), the median survival was 50 and 35 months, respectively (P = .07; Fig 1). However, 9 patients are still alive and in response in the IFN-maintained group versus 2 in the unmaintained group.

In conclusion, the majority of randomized studies on IFN maintenance in MM as well as our results demonstrate that IFN maintenance significantly prolongs the response duration phase in MM patients responsive to previous induction therapy, whereas the efficacy on survival prolongation is less clear. Despite the uncertain effect on survival duration, IFN maintenance is still appropriate in responding myeloma patients, because delaying relapse appearance allows a higher quality of life in patients with MM. Nevertheless, accurate quality of life evaluation is required in these patients to confirm this assumption.