Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents

Abstract

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.

Reduction of serum free light chains predict renal recovery

“…This is likely to translate to the time to renal recovery. In line with other series which used novel chemotherapy agents in this setting [6,7], Matsue et al [1] report a high rate of independence of dialysis. However, the median time to independence of dialysis, 2 months, is uncharacteristically long for an acute kidney injury.…”

Pathogenesis and treatment of renal failure in multiple myeloma

“…In a single center retrospective series, newly diagnosed myeloma patients presenting with acute renal failure were treated with such regimens resulting in a reversal rate of 73%. 38 This rate is higher compared to other series, which included alkylating-based regimens containing standard dose steroids. 1,2 Patients were divided into two groups who received VAD, VAD-like regimens, melphalan plus high-dose dexamethasone or high-dose dexamethasone alone (group A) or high-dose dexamethasone plus thalidomide and/or bortezomib (group B).…”

“…In a series of 20 patients with relapsing myeloma who received thalidomide with or without dexamethasone, renal function was recovered in 12 out of 15 responding patients, but no improvement was observed in patients who were refractory to thalidomide with or without dexamethasone therapy. 56 Kastritis et al 38 also observed reversal of renal failure with thalidomide, in combination with high-dose dexamethasone with or without bortezomib, in 80% of previously untreated patients. Although in most series the toxicity of thalidomide is not different among patients with different levels of renal function, a recent report indicates that severe neuropathy, constipation, lethargy and bradycardia are more frequent in patients with a serum creatinine X3 mg per 100 ml.…”

“…However, in other series, reversal of renal failure was not associated with a superior outcome when compared with cases of patients with sustained renal impairment. 1,38 Patients who present with acute renal failure have increased early mortality, reaching up to 30% within the first two months in some series. 2,37 Furthermore, renal impairment may adversely affect the outcome of myeloma patients in various ways.…”

“…1,2,5,38,46 Conventional chemotherapy with alkylating agents, such as melphalan prednisone (MP), results in moderate rates of renal function recovery, whereas it is complicated by the need for dose adjustment, which may in turn result in suboptimal treatment. 54 In the study of Alexanian et al, 1 after administration of chemotherapy with alkylating agents, doxorubicin and steroids, 51% of patients recovered renal function (defined as a sustained decrease of creatinine o1.4 mg per 100 ml) within a median of 1.2 months.…”