TREATMENT OF MULTIPLE-MYELOMA ACCORDING TO THE EXTENSION OF THE DISEASE - A PROSPECTIVE, RANDOMIZED STUDY COMPARING A LESS WITH A MORE AGGRESSIVE CYTOSTATIC POLICY

The purpose of the study was to ascertain whether the prognostic signi ficance of staging in multiple myeloma (MM) is influenced by the aggre ssiveness of effective induction treatment and/or by continuing or dis continuing maintenance chemotherapy. Patients with untreated stage I M M (defined according to Durie and Salmon) were randomised between bein g followed without cytostatics until the disease progressed and receiv ing six courses of melphalan and prednisone (MP-P) just after diagnosi s; stage II patients were uniformly treated with MPH-P and stage III p atients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiv ing additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until r elapse. With resistant, progressive or relapsing disease, patients ori ginally treated with MPH-P for induction received combination chemothe rapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Co mbination chemotherapy was more myelotoxic than MPH-P and, in particul ar, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Pro gression of disease was statistically similar in stage I patients who were initially left untreated and in those who received MPH-P just aft er diagnosis; median duration of first response was similar in stage I II patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter t he median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 m onths in stage II and was 24.3 months in stage III patients, still ind ependent of both induction and post-induction policies. In MM, the sig nificance of staging for survival is independent of both the aggressiv eness of induction policy and of continuing or discontinuing maintenan ce chemotherapy after the maximal tumour reduction has been achieved. Both MPH-P and the association of PTC, VCR and P are effective in indu cing first response and also second response in patients failing on th e alternative regimen, but PTC-VCR-P causes more side-effects. Thus, t he overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early disease.