Prognostic factors with high-dose melphalan for refractory multiple myeloma

Abstract

High doses of melphalan (HDM) and dexamethasone were administered to 43 patients with advanced multiple myeloma, 36 of whom were refractory to both standard melphalan-prednisone and vincristine-adriamycin-dexamethasone (VAD). Forty-four percent responded with > 75% reduction in calculated tumor mass, including three patients who achieved a complete remission. The response rate to HDM was 56% in 18 relapsing patients and 50% in 12 patients with < 12 months of primary drug resistance, but it was only 23% among the remaining 13 unresponsive patients. A high early mortality rate of 30% was confined to 26 patients with either poor performance (Zubrod > 1) or impaired renal function (creatinine > 1.4 mg%). When this toxic treatment was given to the 21 patients with good performance (Zubrod < 2) whose disease lacked high serum lactic dehydrogenase (= 500 U/L) as a recently recognized feature of high-grade myeloma, a superior median survival of 18 months was obtained as opposed to only 3 months for the 22 remaining patients (P < .001). Thus, when employed in a timely fashion, HDM overcomes resistance to standard chemotherapy and VAD and benefits selected patients with advanced myeloma.