COMBINATION CHEMOTHERAPY, GLUCOCORTICOIDS, AND INTERFERON-ALFA IN THETREATMENT OF MULTIPLE-MYELOMA - A SOUTHWEST-ONCOLOGY-GROUP STUDY

Purpose: Standard therapy for multiple myeloma consists of cytotoxic c hemotherapy plus glucocorticoids. Interferon (IFN) alfa maintenance is reported to prolong chemotherapy-induced remissions and survival. Thi s study evaluates induction chemotherapy, glucocorticoids, and interfe ron maintenance in myeloma. Patients and Methods: Five hundred twenty- two previously untreated myeloma patients were randomized to three che motherapy regimens with differing glucocorticoid intensities. Patients who achieved remission were randomized to receive IFN or observation until relapse. Patients who failed to respond to chemotherapy received IFN alfa plus dexamethasone (DEX). Results: Five hundred nine patient s were eligible for induction chemotherapy. Chemotherapy with higher d ose intensity glucocorticoids yielded higher response rates and improv ed survival (P = .02 for the three-group comparison; P < .05 for each higher glucocorticoid arm v vincristine, melphalan, cyclophosphamide, and prednisone alternating with vincristine, carmustine [BCNU], doxoru bicin, and prednisone [VMCP/VBAP]). One hundred ninety-three patients who achieved remission were randomized to receive IFN alfa 3 MU three times weekly or observation. IFN was not superior to observation for r elapse-free (P = .95) or overall survival (P = .39) from start of main tenance. Eighty-eight induction failures received 5 MU of IFN three ti mes weekly plus DEX. Patients who received IFN/DEX had a median surviv al duration of 48 months from start of IFN/DEX. Conclusion: Higher-dos e glucocorticoids increases frequency of response to chemotherapy and prolong survival in myeloma. IFN maintenance with the dose schedule us ed in this trial did not prolong relapse-free or overall survival. We cannot exclude a small effect of IFN, as most individual trials do not have sufficient statistical power. Meter-analysis of randomized trial s evaluating IFN maintenance in myeloma might be of value. While IFN a ppeared ineffective, addition of higher-dose glucocorticoids improved outcome in myeloma.