Adding Cyclophosphamide to Bortezomib/Dexamethasone in Patients With Multiple Myeloma and Acute Kidney Injury From Cast Nephropathy

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In a French trial reported in the Journal of Clinical Oncology, Bridoux et al found adding cyclophosphamide to bortezomib/dexamethasone offered no benefit for renal recovery of patients with multiple myeloma and initial cast nephropathy not requiring dialysis.

Study Details  

In the multicenter trial, 184 patients with acute kidney injury without need for dialysis were randomly assigned to receive 21-day cycles of bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11) plus dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) without (BD group, n = 92) or with (C-BD group, n = 92) cyclophosphamide (750 mg/m2 on day 1). Patients with < 50% reduction in serum-free light chains after three cycles had either cyclophosphamide (BD group) or thalidomide (C-BD group) added to treatment. The primary endpoint was renal response at 3 months, defined as serum creatinine level ≤ 170 µmol/L or estimated glomerular filtration rate ≤ 40 mL/min/1.73 m2.

Renal Response Rate

At 3 months, renal response was observed in 47 patients (51.1%) in the C-BD group vs 41 patients (44.6%) in the BD group (relative risk [RR] = 0.87, P = .46). At 3 months, hematologic response was reported as very good partial response (free light chain reduction of ≥ 90%) or better in 47 (51.1%) vs 36 (39.1%) patients, respectively (RR = 0.76, P = .14). After one cycle of chemotherapy, serum-free light chain levels ≤ 500 mg/L were achieved in 67 (72.8%) vs 69 (75.0%) of patients (RR = 1.03, P = .87).


  • The addition of cyclophosphamide to bortezomib/dexamethasone did not significantly improve renal response rates.
  • The addition of cyclophosphamide was associated with a higher incidence of serious adverse events.

Adverse Events

Serious adverse events were observed in 43.5% of patients in the C-BD group vs 32.6% of the BD group, with adverse events leading to discontinuation of treatment in 17.4% vs 12.0%. Grade ≥ 3 peripheral neuropathy was observed in two vs three patients, and grade ≥ 3 cytopenia was observed in nine vs five patients. Systemic sepsis or pneumonia was observed in five vs two patients.

The investigators concluded, “This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial cast nephropathy not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with acute kidney injury are fragile, and indication for doublet or triplet regimen should be adapted to frailty.”

Frank Bridoux, MD, PhD, of the Department of Nephrology, CHU Poitiers, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the French Ministry of Health, French National Hospital Program for Clinical Research, Janssen France, and others. For full disclosures of the study authors, visit


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