Intermediate-dose (25mg/m2) IV melphalan for multiple myeloma with renal failure

Multiple myeloma is a malignant plasma cell disorder which still bears a dramatic prognosis. Renal insufficiency is a frequent and severe complication directly related to prognosis. The aim of our study was to establish whether an intermediate dose of intravenous melphalan, 25 mg/m2, could be safely and efficiently administered to patients with multiple myeloma and renal impairment.

Between January 1990 and April 2000, 45 patients with multiple myeloma received a single intravenous dose of melphalan, 25 mg/m2. Survival was analysed, as well as the duration of response and potential toxicity. In addition, a melphalan pharmacokinetic study was performed.

The overall median survival was 45 +/- 43 months after diagnosis. Based on the Cockcroft and Gault formula, 79% patients had renal impairment. For the 28 stage III patients, survival was no different whether renal insufficiency was present or not. Twenty-five out of 34 patients had leukopenia for an average of 13.8 +/- 12 days, and the most frequent adverse effect was infection. The pharmacokinetic study showed that the melphalan area under the curve was positively correlated to the degree of renal insufficiency. However, this was not clinically relevant since patients with the most altered renal function, including those undergoing dialysis, did not present more episodes of leukopenia.

The present study shows that renal impairment is not a contraindication for aggressive myeloma chemotherapy, even for patients undergoing dialysis. Intravenous melphalan, 25 mg/m2, is associated with good survival and acceptable side-effects. A randomised trial seems needed to compare this melphalan dose with standard melphalan/prednisone or combination chemotherapies.