Current treatments for renal failure due to multiple myeloma

ABSTRACT

Introduction: Renal impairment (RI) is one of the most common complication of multiple myeloma (MM). RI is present in almost 20% of MM patients at diagnosis and in 40%-50% of patients during the course of their disease.

Areas covered: Biology along with tools for diagnosis and management of RI are reported in this paper. Papers published in PubMed and reported abstracts up to May 2016 were used.

Expert opinion: Moderate and severe RI increases the risk of early death; thus rapid intervention and initiation of anti-myeloma treatment is essential and improves renal outcomes in RI patients. Bortezomib and dexamethasone triplet combinations are the current standard of therapy for MM patients with acute kidney injury due to cast nephropathy; they offer high rates of both anti-myeloma response and renal recovery. Thalidomide and lenalidomide may be used in bortezomib refractory patients. In the relapsed/refractory setting additional treatment options such as carfilzomib, pomalidomide and monoclonal antibodies are available; however, there is limited data for their effects on patients with RI. High dose melphalan with autologous stem cell transplantation should be considered in otherwise eligible patients with RI. Finally, high cut-off hemodialysis membranes do not seem to offer significant additive effects on anti-myeloma therapies.

KEYWORDS:

• Multiple myeloma
• renal impairment
• cast nephropathy
• novel agents
• bortezomib
• immunomodulatory drugs (IMiDs)
• autologous stem cell transplantation (ASCT)
• high-cut off hemodialysis

Article highlights

• Severe renal impairment is associated with high mortality and morbidity rates, poor outcomes and increased risk of early death.

• Three different conditions of renal impairment can be seen in a myeloma patient: i) functional renal insufficiency which will rapidly improve after appropriate symptomatic measures; ii) acute kidney injury, usually due to myeloma cast nephropathy and inaugurating the disease or revealing a relapse and iii) chronic kidney disease (CKD), where myeloma may be not the main cause.

• Immediate initiation of treatment and prompt diagnostic procedures are the key to ensure better outcomes.

• Bortezomib-based regimens are recommended for the management of myeloma patients with renal impairment.

• High dose dexamethasone is associated with quicker renal responses.

• In patients with advanced disease, triplet therapy is recommended combining bortezomib with dexamethasone and another agent such as thalidomide or cyclophosphamide.

• Immunomodulatory drugs (lenalidomide or pomalidomide), novel proteasome inhibitors (carfilzomib) or monoclonal antibodies (elotuzumab or daratumumab) may be also used in patients who are not able to receive bortezomib.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded