Renal impairment is not an independent adverse prognostic factor in patients with multiple myeloma treated upfront with novel agent-based regimens.

Abstract Renal impairment (RI) is a common presenting complication of multiple myeloma associated with significant morbidity and early mortality, while it has been associated with inferior survival in patients treated with conventional regimens. We assessed the impact of RI in 203 unselected consecutive patients treated upfront with novel agents (thalidomide, lenalidomide, bortezomib). RI was assessed by the estimated glomerular filtration rate (eGFR). RI (eGFR <60 mL/min) was present in 93 (45.8%) of patients at diagnosis and was associated with advanced age, advanced International Staging System (ISS) stage, poorer performance status, hypercalcemia, urine Bence-Jones proteinuria, anemia and thrombocytopenia. Myeloma response rates were similar for patients with or without RI. In univariate analysis RI was associated with shorter survival and a higher rate of early death (7% vs. 3.5%); however, when adjusted for other prognostic factors, RI was not independently associated with survival. In conclusion, in unselected newly diagnosed patients treated with novel agent-based therapies, RI is not independently associated with inferior survival, probably due to the significant activity of novel agents even in the context of RI.

Successful Treatment of a Severe Case of Fournier's Gangrene Complicating a Perianal Abscess.

A 67-year-old male patient with diabetes mellitus and nephritic syndrome under cortisone treatment was admitted to our hospital with fever and severe perianal pain. Upon physical examination, a perianal abscess was identified. Furthermore, the scrotum was gangrenous with extensive cellulitis of the perineum and left lower abdominal wall. Crepitations between the skin and fascia were palpable. A diagnosis of Fournier's gangrene was made. He was treated with immediate extensive surgical debridement under general anesthesia. The patient received broad-spectrum antibiotics, and repeated extensive debridements were performed until healthy granulation was present in the wound. Due to the fact that his left testicle was severely exposed, it was transpositioned into a subcutaneous pocket in the inner side of the left thigh. He was finally discharged on the 57th postoperative day. Fournier's gangrene is characterized by high mortality rates, ranging from 15% to 50% and is an acute surgical emergency. The mainstay of treatment should be open drainage and early aggressive surgical debridement of all necrotic tissue, followed by broad-spectrum antibiotics therapy.

Reversibility of renal failure in newly diagnosed patients with multiple myeloma and the role of novel agents.

The purpose of this analysis was to assess the effect of novel agent-based regimens on the improvement of renal impairment (RI) in newly diagnosed patients with multiple myeloma. Ninety-six consecutive patients with RI received conventional chemotherapy (CC)-based regimens (n=32), IMiDs-based regimens (n=47) or bortezomib-based regimens (n=17) as frontline therapy. Improvement of RI was more frequent in patients treated with novel agents (79% in IMiD- and 94% in bortezomib-treated groups versus 59% in CC-treated group; p=0.02). Bortezomib-based regimens and CrCl>30 ml/min at baseline independently correlated with a higher probability of at least renal partial response (PRrenal) and with a shorter time to PRrenal or better. Thus bortezomib-based regimens may be the preferred treatment for newly diagnosed myeloma patients with RI.

Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment.

OBJECTIVES: Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. PATIENTS & METHODS: Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1-6). Lenalidomide was administered on days 1-21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1-4 and 15-18 for the first four cycles and only on days 1-4 thereafter. RESULTS: Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. CONCLUSIONS: We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI.

Reversibility of renal impairment in patients with multiple myeloma treated with bortezomib-based regimens: identification of predictive factors.

PURPOSE: Renal impairment is a frequent complication of multiple myeloma (MM) and is associated with significant morbidity and increased early death rate. Bortezomib is active and well tolerated in patients with MM who present or develop renal impairment. PATIENTS AND METHODS: We analyzed 46 consecutive patients who presented with renal impairment in order to evaluate the impact of bortezomib on the improvement of renal function and to identify predictive factors associated with renal response. All patients received bortezomib with dexamethasone with or without other agents. RESULTS: Renal response was documented in 59% of patients within a median of 11 days (range, 8-41 days). Two of 9 patients who required dialysis became dialysis independent. A complete renal response (CRrenal) was documented in 30% of patients. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Patients with light chain-only myeloma had a higher probability of achieving a renal response, and previously untreated patients had a higher probability for complete resolution of renal impairment, while light chain-only myeloma was independently associated with a shorter time to renal response. The degree of renal impairment was not predictive of the probability for renal response or CRrenal; however, in a subset of patients for whom cystatin C was available, a baseline cystatin C > 2 mg/L or cystatin C calculated estimated glomerular filtration rate < 30 mL/min were associated with a lower probability of CRrenal. CONCLUSION: We conclude that bortezomib-based regimens may improve renal function in the majority of myeloma patients with renal impairment.

Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens.

UNLABELLED: Renal failure is a common feature of multiple myeloma and a major management problem. However there is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents such as bortezomib when administered to newly diagnosed or relapsed/refractory patients with renal failure. PATIENTS AND METHODS: We evaluated 20 consecutive patients with newly diagnosed or relapsed/refractory multiple myeloma and renal failure, defined as a serum creatinine >or= 2 mg/dl. All patients received bortezomib with dexamethasone or in combination with other agents (thalidomide, doxorubicin or melphalan). RESULTS: Reversal of renal failure was documented in 40% of all patients and the median time to reversal was 17 days. Moreover 10 patients (50%) had 50% decrease in serum creatinine and the median time to decrease was 35 days. Some decrease of creatinine was documented in 85% of patients. The objective response rate was 65%. Toxicities were similar to those seen in myeloma patients without renal failure. CONCLUSIONS: Bortezomib based regimens can be administered to myeloma patients with renal impairment and their toxicity and efficacy are similar to those observed in patients without renal impairment. Moreover, bortezomib-based regimens induce improvement of serum creatinine in most patients and reversal of renal failure in approximately one-third.

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

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.