Bortezomib Effective Induction Therapy for Multiple Myeloma Patients With Renal Failure

Ball-and-stick model of bortezomib.

Induction treatment with bortezomib prior to undergoing autologous stem cell transplant (auto-SCT) resulted in superior outcomes in transplant-eligible patients with multiple myeloma with end-stage renal failure compared with a standard regimen plus high-dose chemotherapy, according to the results of a retrospective study published in Bone Marrow Transplantation.

“Approximately 30% of patients with newly diagnosed multiple myeloma present with renal insufficiency,” wrote Iris Breitkreutz, MD, of Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany, and colleagues. “Before starting treatment, between 1% and 13% of patients require hemodialysis and this cohort has been reported to have particularly poor outcomes.”

Although traditionally these patients had been thought to not be eligible for myeloablative chemotherapy, recent research has shown that patients with myeloma and end-stage renal disease requiring hemodialysis who are treated with high-dose chemotherapy and auto-SCT have rates of toxicity and survival similar to those of patients with normal kidney function.

In this study, Breitkreutz and colleagues sought to evaluate outcomes in these patients when treated with bortezomib. They evaluated the outcomes of 27 consecutive patients with newly diagnosed multiple myeloma who received first-line induction therapy followed by stem cell mobilization, high-dose chemotherapy, and auto-SCT between 1997 and 2011. All patients had dialysis dependency due to multiple-myeloma related renal failure.

The majority of patients had been treated with bortezomib, doxorubicin, dexamethasone (PAD; n = 12), or vincristine, doxorubicin, dexamethasone (VAD; n = 11), or a VAD-like regimen (n = 1). All patients received cyclophosphamide, doxorubicin, and dexamethasone followed by G-CSF for stem cell mobilization, and high-dose chemotherapy with melphalan.

The researchers measured renal function based on creatinine clearance after treatment and found that patients treated with bortezomib had a 6.1-month median time to recovery of renal function compared with 17.1 months for patients treated with a standard regimen; however, the difference was not significant (P = .38).

Patients treated with bortezomib had a significantly higher overall response rate prior to auto-SCT compared with the standard regimen (83.3% vs 35.7%; P = .021). In addition, this increased response rate was retained beyond 100 days post-transplant (100% vs 58.3%; P = .014).

Finally, data showed that patients treated with bortezomib induction also had longer survival rates. The median event-free survival has not yet been reached in the bortezomib group compared with 28 months in the VAD or VAD-like groups (HR = 0.39; P = .04) with a median follow-up of 53 months for bortezomib and 84 months for VAD.

Median overall survival has not been reached for patients treated with bortezomib compared with 35 months for those treated with a standard regimen (HR = 0.51; P = .21).

“Although the survival difference is not statistically significant, these data underline the promising efficacy of bortezomib for patients with end-stage renal failure when administered as first-line induction therapy followed by high-dose therapy and auto-SCT,” the researchers wrote.