Successful Treatment with Bortezomib in Combination with Bendamustine and Prednisone of Patients with Newly Diagnosed/Untreated Multiple Myeloma and Light Chain Induced Renal Failure

Renal impairment is one of the most severe complications of Multiple Myeloma (MM) at diagnosis. These patients are at increased risk for infections and have a significantly worse prognosis. Small phase I/II studies suggest that treatment with chemotherapy and/or new substances results in recovery of renal function in up to 25%. The window of opportunity to reverse renal impairment is rather small, making an immediate and highly active treatment strategy mandatory. Bortezomib as well as Bendamustine have turned out to be effective, rapid action drugs in the treatment of MM. Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks of DNA, and shows only partial cross resistance with other alkylating drugs.

Between June 2006 and May 2011, 18 patients (median age 69; range 43 – 86 years) with newly diagnosed/untreated MM and renal insufficiency (creatinine clearance < 35 ml/min) were treated with Bendamustine 60 mg/qm day 1 and 2, Prednisone 100 mg on day 1, 2, 4, 8 and 11, and Bortezomib 1.3 mg/qm on day 1, 4, 8 and 11 (BPV). Cycles were repeated every 21 days up to the stage of maximum response or disease progression. MM response was assessed using IMWG criteria modified to include near complete response (nCR) and minimal response (MR). Eight patients were on dialysis at the time of diagnosis.

Fifteen patients (83%) responded after at least one cycle of chemotherapy with three sCR, five nCR, five VGPR, and two PR. With a median follow up of 17 months, PFS at 12 months was 57 % and OS was 61 %. The median number of the BPV-treatment cycles was 2 (1–5) cycles. The myeloma protein decreased rapidly, reaching the best response after the first cycle in 4 patients and after the second cycle in a further 7. Six patients showed a complete remission of the kidney function (creatinine clearance > 60 ml/min) and in seven patients a partial remission (creatinine clearance > 30 ml/min) was attained. Transient grade 3 – 4 neutropenia was reported in one patient, and grade 3 – 4 thrombocytopenia occurred in 6 patients. One patient experienced a new grade 3 polyneuropathy.

These results indicate that the combination of Bortezomib, Bendamustine and Prednisone is effective and tolerated in patients with newly diagnosed/untreated MM and renal failure.

Pönisch:Mundipharma: Honoraria, Research Funding. Niederwieser:Mundipharma: Research Funding.