The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma - Phase III Eastern Cooperative Oncology Group clinical trial EST 9486

BACKGROUND, Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Gro up (ECOG) study suggested that the rates of complete response (CR) and surv ival were increased with a regimen that alternated IFN with chemotherapy. T he current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiC y) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS, From February 1988 to May 1992, the ECOG entered previously untrea ted patients with active multiple myeloma on a study in which they were ran domized to VBMCP (vincristine 1.2 mg/m(2) administered intravenously [i.v.] on Day 1, BCNU 20 mg/m(2) i.v. on Day 1, melphalan 8 mg/m(2) administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m(2) i.v. on Dap 1, and prednisone 40 mg/m(2) p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(alph a 2), the latter given at 5 Mu/m(2) 3 times a week starting on Day 22 of ea ch 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 y ears were also randomized to a third treatment that substituted cyclophosph amide 600 mg/m(2) i.v. on Days 1-4 and prednisone 100 mg/m(2) p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS, Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients o f 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of th e three regimens revealed no significant difference in the rates of surviva l or objective response (OR). However, CRs were increased among patients tr eated with VBMCP + rIFN(alpha 2) compared with VBMCP alone (18% vs. 10%, P = 0.03). Patients treated with VBMCP + rIFN(alpha 2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.03 5). There was a greater response rate with the IFN regimen among elderly pa tients (OR and CR = 67% and 31%, respectively) and patients with immunoglob ulin A (IgA) myeloma (OR and CR = 83% and 29%, respectively). Severe infect ions were seen as often with VBMCP as with VBMCP + rIFN(alpha 2) (13% vs. 1 5%), but they were more frequent with VBMCP + HiCy (25%). CONCLUSIONS, VBMCP + rIFN(alpha 2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(alpha 2) induction therapy to produce CR and more durable responses, as well as its activity in older patients a nd in those with IgA myeloma, suggest that this therapy has important biolo gic activity in myeloma and merits further clinical investigation. (C) 1999 American Cancer Society.