clinicaltrials.gov Identifier: NCT01208818.

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PURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m melphalan is a beneficial procedure for MM patients with renal failure.

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