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.

Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with multiple myeloma: long term follow up and disease control after subsequent treatments.

There are limited data regarding the long term follow up after thalidomide based regimen and the outcome of patients when they progress and they receive further treatment. We reassessed our original series of 43 patients with previously treated multiple myeloma who had received a pulsed cyclophosphamide, thalidomide, dexamethasone (CTD) regimen. Among the 43 patients, 14 did not respond to pulsed CTD and 29 (67%) achieved at least a partial response. The median PFS for all patients was 10 months. After a median follow up of 24 months (range 1 - 62), the 3 year PFS is 14% and 3 patients remain off treatment and without progression for 55+, 55+ and 56+ months respectively. Moreover, 28% of patients who progressed after CTD achieved a partial response after subsequent treatment which included thalidomide, bortezomib or lenalidomide. The median PFS of these patients was 5 months and the 1 year PFS was 20%. Furthermore, 31% of patients who had responded to CTD and then progressed (CTD sensitive) responded to subsequent treatment. We conclude that some patients enjoy long responses after CTD and that several patients who progress after CTD may respond to treatment with a novel agent-based regimen.