Thalidomide-Dexamethasone as Induction Therapy Prior to Autologous Stem-Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma and Renal Failure.

Abstract 4934 Multiple myeloma (MM) patients presenting with renal feature at disease onset should not be excluded from high-dose therapy programs; seeking novel effective and non-nephrotoxic induction regimens is thus mandatory in order to maximize the reduction of tumor burden prior to transplant. From May 2002 to February 2008, 31 newly diagnosed MM patients (18 male, 13 female, median age 60 years) with symptomatic MM and renal failure, defined as creatinine clearance '50ml/min, were enrolled in a clinical trial aimed at evaluating the efficacy and the feasibility of a thalidomide-based regimen as induction therapy in preparation to autologous stem cell transplantation. Sixteen patients had a more severe renal impairment (creatinine clearance '30ml/min) and 7 of them were in chronic hemodyalisis. After informed consent, patients received four months of combined oral thalidomide (thal) (100mg/day for two weeks and 200mg/day thereafter) and dexamethasone (dex) (40mg/day on day 1-4, 9-11, 17-20/28 days on odd cycles and on day 1-4 on even cycles); peripheral blood stem cell collection was thus to be performed after priming with high-dose cyclophosphamide + G-CSF or G-CSF alone; a single or double autologous stem cell transplantation was then to follow, upon preparation with high-dose melphalan. After induction, a PR or better was obtained in 23 patients (74%), with 8 patients (26%) achieving a VGPR or better. No difference in response rate was observed in patients with a baseline creatinine clearance ≥30ml/min (86%) or < 30ml/min (62%). An improvement in renal function was more frequently observed in patients achieving ≥ PR (82% vs. 37% in patients obtaining < PR, p =0.04). Twenty-six patients underwent peripheral blood stem cell mobilization; in 17 of them (65%) the procedure was successful resulting in the collection of > 4 × 106 CD34+ cells/kg. Fifteen patients received a double autologous stem cell transplantation while a single transplant was performed in four patients. Overall, median event-free survival was 30 months, and median survival has not been reached, upon 32 months median follow-up. Toxicity profile of thal-dex was comparable to that observed in patients with a normal renal function. In conclusion, our data show that thal-dex can be safely administered in patients with newly diagnosed MM and renal failure. given the relationship between recovery of renal function and response to induction treatment, more intensive thal + bortezomib-including regimens could be potentially useful in order to rescue a higher number of patients. Disclosures Off Label Use: Thalidomide plus dexamethasone in newly diagnosed multiple myeloma.