Results of a small German study indicate that the combination regimen of Velcade, Treanda, and prednisone is effective and well tolerated in newly diagnosed multiple myeloma patients with kidney impairment.
The majority of patients showed improved kidney function after treatment. The study investigators point out that patients responded rapidly, which may have prevented the development of irreversible kidney failure.
Based on their findings, the investigators recommend that the combination therapy be investigated further in larger clinical trials.
Impaired kidney function is a severe complication of multiple myeloma and affects 20 percent to 50 percent of myeloma patients at the time of diagnosis. It is primarily caused by the toxic effects of monoclonal light chain proteins, which are produced by myeloma cells.
Prior studies have demonstrated that treatment with certain chemotherapy or novel agents can lead to kidney recovery in up to 50 percent of treated patients. According to the current study investigators, reversing kidney failure requires a quick and effective course of therapy that significantly impedes the production of light chains.
Both Velcade (bortezomib) and Treanda (bendamustine) have both previously been studied as viable treatment options for patients with impaired kidney function.
Velcade has been shown to be very effective in this patient population. In addition, Velcade is not filtered out through the kidneys and therefore does not further damage them.
Treanda, which is already approved for the treatment of chronic lymphocytic leukemia and certain lymphomas, is currently being investigated as a treatment for multiple myeloma. A previous retrospective study demonstrated the effectiveness of Treanda with thalidomide (Thalomid) and dexamethasone (Decadron) in the treatment of myeloma patients with end-stage kidney disease.
In the current study, researchers at the University of Leipzig in Germany retrospectively analyzed data from 18 newly diagnosed myeloma patients with moderate to severe kidney impairment who were treated with a combination of Velcade, Treanda, and prednisone between 2006 and 2011. The median patient age was 69 years.
All patients received 60 mg/m2 of Treanda on days 1 and 2; 100 mg of prednisone on days 1, 2, 4, 8, and 11; and 1.3 mg/m2 of Velcade on days 1, 4, 8, and 11 of a 21-day treatment cycle. For patients on dialysis, the same dosages of Treanda and Velcade were administered 30 minutes after the end of dialysis.
Patients continued treatment until they reached a maximum response, showed excessive side effects, or demonstrated disease progression.
Overall, patients received a median of two treatment cycles.
The researchers found that 83 percent of patients achieved at least a partial response, with 17 percent reaching a complete response, 28 percent a near complete response, and 28 percent a very good partial response.
According to the study investigators, these results are comparable to those from a prior study evaluating treatment with Velcade, melphalan, and prednisone. In that study, 74 percent of patients with severe kidney dysfunction responded to treatment, with 37 percent reaching a complete response.
In the current study, the median time to best response was 42 days. Eighty percent of patients showed a decrease in free light chain levels of at least 50 percent after a median of four days.
Seventy-two percent of patients showed improvements in kidney function within a median of 21 days; 50 percent of patients who were on dialysis recovered enough kidney function to end dialysis treatment.
At 18 months post treatment, the progression-free survival rate was 57 percent and the overall survival rate was 61 percent.
The most common severe side effects included low white blood cell counts (33 percent), low platelet counts (33 percent), anemia (28 percent), and bacterial infections (28 percent). Severe peripheral neuropathy, a common side effect of Velcade characterized by pain, tingling, or loss of sensation in the extremities, was observed in 6 percent of patients.
According to the investigators, side effects in this patient population were similar to those in patients with normal kidney function treated with other Velcade combinations.
For more information, please see the study in the Journal of Cancer Research and Clinical Oncology (abstract).