There is no difference in efficacy between triplet vs doublet bortezomib-based therapies to treat patients with initial myeloma cast nephropathy and acute kidney injury without a dialysis requirement, according to research published in the Journal of Clinical Oncology.

Frank Bridoux, MD, PhD, and colleagues in the MYRE study group conducted a multicenter controlled trial to compare the tolerance profile and renal recovery of doublet therapy, which consisted of bortezomib with dexamethasone (BD), and the triplet combination, which was cyclophosphamide with BD (C-BD).

Patients were randomly assigned to receive either BD or C-BD after initial treatment with dexamethasone or methylprednisolone during a screening period. Following 3 cycles with BD or C-BD, patients who experienced a less than 50% reduction in serum free light chains (sFLCs) received treatment with cyclophosphamide (BD arm) or thalidomide (C-BD arm).

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The primary study endpoint was renal response at 3 months. Renal response was characterized as a serum creatinine level ≤170 mmol/L and/or an estimated glomerular filtration rate ≥40 mL/min/1.73 m2 or higher.

Each treatment arm enrolled 92 patients. Median baseline serum creatinine levels were 305.5 mmol/L in the BD treatment group and 273.5 mmol/L in the C-BD group. After 3 months of therapy, the renal response rates were similar between the BD group and the C-BD group (44.6% vs 51.1%, respectively; relative risk [RR], 0.87; P =.46).

Very good partial response (VGPR) was defined as a reduction in sFLCs of 90% or more. At 3 months, VGPR or better was seen in 39.1% of patients given BD and 51.1% of patients given C-BD (RR, 0.76; P =.14). A level of sFLCs of ≤500 mg/L was demonstrated after 1 cycle of treatment for 75.0% of patients given BD and 72.8% of patients given C-BD.

Fatalities were reported in 24 patients from the BD group and in 26 from the C-BD group over the course of the study (P =.99). At 12 months, 19 patient deaths were reported; 10 deaths were attributed to myeloma progression (6 patients receiving BD and 4 receiving C-BD). Deaths at 12 months relating to infection occurred in 3 patients receiving C-BD and in no patients receiving BD. At a median follow-up of 27 months, similar numbers of patients in each arm had changed to other treatments (43 in the BD arm and 42 in the C-BD arm).

The study investigators concluded that C-BD did not confer a benefit over BD in renal recovery for the patient population in this study. However, they also suggested the choice of doublet or triplet bortezomib-based therapy may be based on a patient’s fitness.


Bridoux F, Arnulf B, Karlin L, et al. Randomized trial comparing double versus triple bortezomib-based regimen in patients with multiple myeloma and acute kidney injury due to cast nephropathy [published online June 23, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.00298