Viewpoint on the impact of interferon in the treatment of multiple myeloma: benefit for a small proportion of patients?

Abstract

Interferon-alpha (IFN-alpha) generally inhibits myeloma cell growth. However, a growth stimulatory effect for myeloma cells has also been reported. In patients with untreated multiple myeloma (MM) IFN-alpha, used as a single agent, produced an objective response rate ranging from 10 to 25%. In previously untreated patients: (1) the time to response is short, (2) the median duration of response is similar to the duration of response observed in patients given chemotherapy, and (3) the patients who are more likely to benefit are those with IgA myeloma type. Concerning the results of IFN-alpha given as a single agent in relapsing and resistant MM, they are poor, with a response rate ranging between 10-20%. The combination of high-dose glucocorticoids and IFN-alpha for relapsing/resistant patients produced controversial results. Some studies showed an increased response rate and/or longer survival with chemotherapy plus IFN-alpha versus chemotherapy alone in previously untreated patients. In contrast, most reports did not show a significant increase in response rate or survival benefit by adding IFN-alpha to the initial chemotherapy. Perhaps the most encouraging role for IFN in MM is as maintenance therapy in patients responding to first line treatment (ie conventional chemotherapy followed or not by high-dose intensification/autotransplantation). In spite of that, several reports failed to show longer response duration. The majority of studies have shown a modest but significant prolongation in response duration in favour of the IFN arm. However, most of these studies have failed to show a significant survival advantage with IFN maintenance. A meta-analysis, by the Myeloma Trialists' Collaborative Group in Oxford, based on the individual data from 4012 patients included in 24 randomized trials (induction and/or maintenance) has shown that IFN produced a moderate improvement in relapse-free survival and a minor improvement in overall survival. In summary, the only role of IFN in MM is as maintenance treatment after a response is achieved. However, looking at the published data, it seems that the vast majority of patients do not benefit from IFN maintenance, while a small proportion of them, in the range of 5-10%, obtain a significant prolongation in event-free survival and overall survival. Unfortunately, there are no predictive factors that can identify the patients who are likely to benefit from IFN maintenance.