Safety and Efficacy of Bortezomib in Multiple Myeloma Patients with Renal Failure Requiring Dialysis.

Introduction: Bortezomib (VELCADE^®), a novel proteasome inhibitor, is currently approved for treatment of multiple myeloma (MM) patients in first relapse in the US and EU. At presentation, up to 50% of patients with MM have decreased creatinine clearance, and 20–30% have concomitant renal failure. Although bortezomib has been reported to be safe and effective in patients with renal insufficiency and creatinine clearance as low as 14 mL/min, there is currently little information on its use in patients with advanced renal failure requiring hemodialysis. We conducted a multicenter, retrospective review to investigate the safety and efficacy of bortezomib in renal failure patients requiring hemodialysis.

Patients and Methods: Patients were identified by the treating physicians at the participating centers. MM patients with advanced renal failure with or without hemodialysis support who were treated with bortezomib or a bortezomib containing regimen were eligible. Patients had to be ≥ 18 years. Demographic data, dose of bortezomib, response (by EBMT criteria) and duration of response as well as available toxicity data were to be collected for a maximum of 30 patients.

Results: Thus far, all data are available for 15 MM patients. The median age was 59 years (range 51–78) and 60% were male. The MM type was IgG in 7 patients, light chain disease in 5, IgA in 2, and IgD in 1. The MM subtype was kappa in 6 patients, lambda in 3, and not specified in 6. All patients had relapsed after a median of 2 prior therapies (range 1–5). All had advanced renal failure while 11 patients were receiving hemodialysis at the time of bortezomib administration. Bortezomib was given after hemodialysis in 10 patients; the timing was not specified in 1. One patient was not evaluable for response. Of the 14 evaluable patients, 2 (14%) achieved a complete response (CR), 1 (7%) had a near CR (nCR) and 2 (14%) had a partial response (PR) for an overall response rate of 36%. Five patients (36%) had stable disease and 4 (27%) had progressive disease. The response durations for the 2 patients achieving CR were 12+ and 17+ months, and for the patient with nCR was 9+ months. The duration of response for those with PR were 2 and 12+ months. One patient died due to progressive disease. One patient (7%) discontinued due to neuropathic pain at cycle 4, and 2 patients (14%) had doses held due to peripheral neuropathy, both at cycle 4. Bortezomib was otherwise generally well tolerated. One patient scheduled for hemodialysis achieved a CR with normalization of renal function without needing dialysis.

Conclusion: Although there is no pharmacokinetic (PK) data available and the number of patients studied is relatively small, the information gathered from this study suggests that bortezomib can be given safely to patients with renal failure on hemodialysis who may benefit from this therapy. A formal prospective study with PK is warranted in this patient population to establish a comprehensive safety and efficacy profile and this is ongoing under the auspices of the NCI.