MRC trial of α2b-interferon maintenance therapy in first plateau phase of multiple myeloma

Plateau phase has been achieved in 64% of all newly diagnosed patients with multiple myeloma treated with the ABCM (adriamycin, BiCNU, cyclophosphamide and melphalan) regimen in the Medical Research Council (MRC) trials; this stable clinical stage of the disease is associated with no more than minimal symptoms. Several studies have found that alpha-interferon (alpha-IFN) maintenance therapy increases the duration of plateau phase, but it is less clear if this translates into prolonged survival. We report the effect of alpha-IFN on the duration of plateau phase and overall survival in a trial with 284 patients who were randomized to receive alpha 2b-IFN (Intron-A) or no maintenance therapy during first plateau phase. The minimum follow-up after randomization was 21 months, There was no significant difference in the overall survival between the two treatment groups (chi(2) = 0.32, P = 0.57). There was a trend towards longer relapse-free survival in the patients allocated alpha-IFN, but this trend to longer plateau phase was not statistically significant (chi(2) = 1.62, P = 0.2). Disease progression at relapse on a-IFN appears to be more severe with greater elevations from plateau levels of serum paraprotein (P = 0.006) and beta(2)-microglobulin (P = 0.03) levels. Physicians tended to start chemotherapy sooner after diagnosis of relapse when patients had received alpha-IFN (P = 0.16). Although, in common with most other studies, there is a trend for patients treated with alpha-IFN to have a longer plateau phase, this is counteracted by morbidity attributable to the treatment and a somewhat shortened survival post relapse. Meta-analysis of interferon trials is required to assess whether the minor trend for longer survival in patients maintained on alpha-IFN found in some studies is significant and, if so, the extent of this advantage.