Glomerular filtration rate prior to high-dose melphalan 200 mg/m(2) as a surrogate marker of outcome in patients with myeloma

We correlated age and body surface area corrected glomerular filtration rat e (GFR) at the time of high-dose melphalan (HDM) administration with treatm ent-related toxicity (TT), time to disease progression and survival. Betwee n 8/85 and 6/98, 144 newly diagnosed myeloma patients with a median age of 53 years (range, 31-72) received infusional chemotherapy with vincristine, doxorubicin and methylprednisolone, with/without cyclophosphamide or verapa mil, followed by HDM 200 mg/m(2) and stem cell rescue. An additional patien t received HDM at diagnosis. GFR was below normal in 38 patients (26%). At presentation, patients with low GFR at the time of HDM had higher serum cre atinine, beta M-2, stage III disease, calcium and Bence-Jones proteinuria. Toxic deaths post-HDM were similar in both groups (2/38 (5%) vs. 4/107 (4%) ), though patients with low GFR had more oral mucositis (P < 0.0001), diarr hoea (P = 0.005) and infections (P = 0.04). The response and relapse rates of the 2 groups were not substantially different, but the median overall su rvival (OS) was significantly shorter in patients with low GFR (5.1 vs 7.5 years, P = 0.015). Multivariate analysis showed that a normal GFR and being in CR at the time of HDM were predictive of longer OS. We conclude that in context of high-dose chemotherapy for myeloma, dose of melphalan should no t be modified in patients with low GFR and that early intensive treatment a t relapse may improve results in patients with abnormal renal function. (C) 2001 Cancer Research Campaign.