Current Trends of Renal Impairment in Multiple Myeloma

Abstract

Background: Renal impairment (RI) is a common complication of multiple myeloma (MM). Around 50% of patients with MM have RI at presentation, and up to 5% require dialysis treatment. Severe acute kidney injury (AKI) as a cause of RI is a particular challenge as historically the survival of patients who sustain this complication and require dialysis is very poor. However, in this current period, survival is improving and the focus is on optimum use of novel chemotherapies and the evaluation of extra-corporeal therapies for removal of serum immunoglobulin light chains. Summary: RI in patients with MM is commonly associated with excess monoclonal free light chain (FLC) production; myeloma cast nephropathy is the predominant renal pathology in patients presenting with severe RI secondary to AKI. The majority of patients have mild to moderate RI and recover renal function. However, patients with more severe RI, in particular those with a requirement for dialysis, are less likely to recover renal function. Rapid diagnosis and prompt institution of anti-myeloma therapy is an important determinant of renal function recovery, through targeting early and sustained reduction of involved monoclonal FLC. Novel agents are associated with excellent disease response, and bortezomib is now widely used as a first-line agent in the management of MM in patients with severe RI. Extended haemodialysis using high cut-off dialysers is more effective for extracorporeal removal of FLC than plasma exchange, and clinical trials are in process. High-dose chemotherapy with autologous stem cell transplantation does have a role in patients with severe RI but requires careful patient selection. Key Messages: RI is very common in patients with MM, and renal function recovery is associated with improved clinical outcomes. We summarise the epidemiology of MM in the UK, present the impact of RI and renal function recovery on patient outcome, and describe the current management of MM in western countries. Facts from East and West: (1) A serum creatinine level >2 mg/dl has been reported in 16, 21, 24, and 33% of patients with MM in cohort studies from Japan, Europe, China, and Korea, respectively. A creatinine clearance rate <30 ml/min was observed in 30 and 15% of patients in Chinese and Western MM cohorts, respectively. The commonest cause of severe RI in patients with MM is myeloma cast nephropathy. (2) The efficacy of novel treatments (bortezomib, carfilzomib, thalidomide, and lenalidomide) has predominantly been assessed in Western patients. Bortezomib and dexamethasone are the current standard of care for MM and severe RI in the West. Severe RI is not a contraindication to autologous stem cell transplantation (ASCT). Most of the data are from the West; there are case reports from China describing good outcomes with ASCT. The removal of FLC by high-cut-off hemodialysis is under evaluation in randomized controlled trials (RCTs) in the West. Studies in this area are not yet conducted in China. In China, new treatments, such as bortezomib, are more w...

Cure of Insulin-Dependent Diabetes Mellitus by an Autologous Hematopoietic Stem Cell Transplantation Performed to Control Multiple Myeloma in a Patient with Chronic Renal Failure on Regular Hemodialysis

“…Several studies have shown that VRD regimen is well tolerated and highly effective in the treatment of newly diagnosed MM [16][17][18][19][20][21]. The new novel drugs that include: (1) new immunomodulatory agents such as pomalidomide, (2) next generation proteasome inhibitors such as carfilzomib and ixazomib, (3) histone acetylase inhibitors such as panobinostat, and (4) monoclonal antibodies such as daratumomab and elotuzumab have already shown promising results in the treatment of MM patients [5,22].…”

“…However; age, performance status and renal dysfunction are not exclusion criteria to safe transplantation, but frailty of the patient is a major determinant of eligibility for HSCT [24]. For candidates of auto-HSCT with normal renal function the standard conditioning therapy is high-dose melphalan 200 mg/m 2 , whereas for patients having serum creatinine ˃2 mg/dL, the dose of melphalan should be reduced to 140 mg/m 2 [5,12]. Studies have shown that in adult patients with MM, VRD regimen followed by auto-HSCT has been associated with significantly longer PFS but not OS compared to VRD alone and that auto-HSCT with VRD induction and consolidation followed by lenalidomide maintenance has produced high-quality responses and favorable tolerability in patients with newly diagnosed MM [16,18,22].…”

“…RI is one of the most common complications of MM [5,7,8,11,25]. Between 20% and 50% of patients with newly diagnosed MM present with RI while 40-50% of patients develop RI during the course of the disease [5,7,8].…”

“…Patients with MM having RI can be treated with triplet combinations using either bortezomib-or thalidomide-based regimens [2,[5][6][7][8][9]. Historically, patients with pre-existing chronic kidney disease have been excluded from hematopoietic stem cell transplantation (HSCT) which is a potentially lifesaving therapeutic modality [5,10,11].…”

“…Historically, patients with pre-existing chronic kidney disease have been excluded from hematopoietic stem cell transplantation (HSCT) which is a potentially lifesaving therapeutic modality [5,10,11]. However, high-dose chemotherapy (HDC) followed by HSCT is becoming more widely used in patients with comorbid medical conditions including those with RI [10].…”