Reversibility of Renal Failure in Newly Diagnosed Patients with Multiple Myeloma Treated with High-Dose Dexamethasone Containing Regimens and the Impact of Novel Agents.

Introduction: Approximately 20% of patients with multiple myeloma present with renal failure (RF). It has been reported that with supportive measures and with antimyeloma treatment RF is reversible in 25 to 58% of patients. However, the impact of specific antimyeloma therapies on RF reversibility has not been clarified. Because high dose dexamethasone containing regimens are associated with a rapid myeloma control we performed a study to assess the impact of such regimens on RF reversibility.

Patients and methods: Over the last decade 41 patients with RF, defined as a serum creatinine ≥2 mg/dL at the time of diagnosis, received primary treatment with high dose dexamethasone-based regimens in our Department. All patients were eligible fore assessment of reversibility of RF which was defined as a sustained decrease of serum creatinine to <1.5 mg/dl. Patients were separated into two groups. Group A: 26 patients who received VAD, VAD like regimens, Melphalan-high dose Dexamethasone or high-dose Dexamethasone alone and Group B: 15 patients who received high-dose Dexamethasone with thalidomide, with bortezomib or both.

Results: Patients characteristics included: median age of 65 years, creatinine ≥4 mg/dL in 44%, Bence-Jones proteinuria ≥2 gr/day in 34%, ISS stage III in 76%, light chain only myeloma in 37%. Dialysis was required at presentation in 24% of patients. Response to treatment (EBMT criteria) was documented in 46% of patients of Group A and in 64% of patients of group B. The toxicity profile of novel agents-Dexamethasone combinations was similar to that seen in patients without RF. RF was reversed in 73% of all patients, in 69% of patients in group A and in 80% of patients in group B. After treatment only two patients initially requiring dialysis remained on renal replacement therapy. Multiple variables were assessed for their impact in RF reversibility: serum Creatinine ≥4 mg/dL and Bence-Jones proteinuria≥2 gr/day were associated with significantly lower probability of RF reversal (56% and 54% respectively). RF reversibility rate was 85% in patients who responded to treatment versus 56% in those who did not respond (p=0.046). The median time to RF reversal was 1.9 months for all patients, 2 months for patients of group A and 0.8 months for patients of group B (p=0.005).

Conclusions: RF can be reversed in the majority of patients with newly diagnosed MM when they are treated with high-dose dexamethasone based regimens. Furthermore, normalization of serum creatinine occurs in one half of patients who do not meet criteria for objective response. Novel agents such as thalidomide and bortezomib or both can be safely combined with high dose dexamethasone for the treatment of Myeloma patients who present with RF and are associated with rapid rate of RF reversal.