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

Interferon-alpha (IFN-alpha) generally inhibits myeloma cell growth. Howeve r, 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 in to 25%. In previ ously untreated patients: (1)the time to response is short, (2) the median duration of response is similar to the duration of response observed in pat ients given chemotherapy, and (3) the patients who are more likely to benef it are those with IgA myeloma type. Concerning the results of IFN-alpha giv en as a single agent in relapsing and resistant MM, they are poor, with a r esponse rate ranging between 10-20%. The combination of high-dose glucocort icoids and IFN-alpha for relapsing/resistant patients produced controversia l results. Some studies showed an increased response rate and/or longer sur vival with chemotherapy plus IFN-alpha versus chemotherapy alone in previou sly untreated patients. In contrast, most reports did not show a significan t 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 tie con ventional chemotherapy followed or not by high-dose intensification/autotra nsplantation). In spite of that, several reports failed to show longer resp onse duration. The majority of studies have shown a modest but significant prolongation in response duration in favour of the IFN arm. However, most o f these studies have failed to show a significant survival advantage with I FN maintenance. A meta-analysis, by the Myeloma Trialists' Collaborative Gr oup in Oxford, based on the individual data from 4012 patients included in 24 randomized trials (induction and/or maintenance) has shown that IFN prod uced a moderate improvement in relapse-free survival and a minor improvemen t in overall survival. In summary, the only role of IFN in MM is as mainten ance treatment after a response is achieved. However, looking at the publis hed data, it seems that the vast majority of patients do not benefit from I FN maintenance, while a small proportion of them, in the range of 5-10%, ob tain a significant prolongation in event-free survival and overall survival . Unfortunately, there are no predictive factors that can identify the pati ents who are likely to benefit from IFN maintenance.