No abstract

The role of thalidomide, bortezomib and lenalidomide in multiple myeloma patients presenting with renal impairment was evaluated in 133 consecutive newly diagnosed patients who were treated with a novel agent-based regimen. A significant improvement of renal function (XrenalPR (renal partial response)) was observed in 77% of patients treated with bortezomib, in 55% with thalidomide and in 43% with lenalidomide (P ¼ 0.011). In multivariate analysis, bortezomib-based therapy was independently associated with a higher probability of renal response compared with thalidomide-or lenalidomide-based therapy. Other important variables included eGFR (estimated glomerular filtration rate) X30 ml/min, age p65 years and myeloma response. Patients treated with bortezomib achieved at least renalPR in a median of 1.34 months vs 2.7 months for thalidomide and 46 months for lenalidomide-treated patients (P ¼ 0.028). In multivariate analysis bortezomib-based therapy, higher doses of dexamethasone (X160 mg during the first month of treatment), an eGFR X30 ml/min and age p65 years were independently associated with shorter time to renal response. In conclusion, bortezomib-based therapies may be more appropriate for the initial management of patients with myeloma-related renal failure; however, thalidomide and lenalidomide are also associated with significant probability of improvement of their renal function.

The impact of high dose dexamethasone containing regimens with or without the novel agents thalidomide and bortezomib on the reversal of renal failure (RF) was evaluated in 41 consecutive newly diagnosed patients with multiple myeloma (MM) treated in a single institution. RF was reversed in 73% of all patients within a median of 1.9 months. In patients treated with dexamethasone and novel agents (thalidomide and/or bortezomib) the reversibility rate was 80% within a median of 0.8 months. Severe RF and significant Bence Jones proteinuria were associated with a lower probability of RF reversal. Patients who responded to treatment achieved RF reversal more often than in those who did not (85% versus 56%, p=0.046). In conclusion, RF is reversible in the majority of newly diagnosed MM patients treated with high-dose dexamethasone containing regimens. The addition of novel agents induces a more rapid RF reversal.

In patients with late UTIs, renal scarring is a frequent finding. Scarring may occur even in asymptomatic patients without VUR. The lack of an effect on graft survival may reflect successful intervention with prophylactic antibiotics and surveillance urine cultures. Late recurrent UTIs may be damaging to renal allografts, even in the absence of reflux.

Clinical trials with carfilzomib have indicated a low but reproducible incidence of cardiovascular and renal toxicities. Among 60 consecutive myeloma patients treated with carfilzomib-based regimens who were thoroughly evaluated for cardiovascular risk factors, 12% (95% confidence interval, 3.8%-20%) experienced a reversible reduction of left ventricular ejection fraction (LVEF) by ≥20%, an objective measure of cardiac dysfunction. The incidence of LVEF reduction was 5% at 3 months, 8% at 6 months, 10% at 12 months, and 12% at 15 months, whereas the respective carfilzomib discontinuation rate unrelated to toxicity was 17%, 35%, 41%, and 49%. The presence of any previously known cardiovascular disease was associated with an increased incidence of cardiac events (23.5% vs 7%; = .07), but there was no association with the dose of carfilzomib or the duration of infusion. Re-treatment with carfilzomib at lower doses was possible. Carfilzomib was commonly associated with a transient reduction of estimated glomerular filtration rate (eGFR) but also improved renal function in 55% of patients with baseline eGFR<60 mL/min/1.73 m. Further investigation is needed to elucidate the underlying mechanisms of carfilzomib-related cardiorenal toxicity.