Renal Impairment at Diagnosis in Myeloma: Patient Characteristics, Treatment, and Impact on Outcomes. Results From the Australia and New Zealand Myeloma and Related Diseases Registry

Renal impairment (RI) is a poor prognostic factor in patients with multiple myeloma (MM). Despite improvements in survival with the introduction of novel therapies in recent years, RI remains one of the most common complications with an incidence of 20% to 50% at diagnosis, and approximately 5% to 10% of MM patients are dialysis-dependent.1-3 The most common cause of RI in MM is cast nephropathy, in which excess light chains form aggregates and casts resulting in tubular blockage and inflammation.4-6 Other factors include toxic effects of light chains on the basement membranes of glomeruli and proximal tubules, interstitial nephritis, amyloid deposition, and plasma cell infiltration, which are further exacerbated by hypercalcemia, dehydration, hyperuricemia, and nephrotoxic drugs. Patients with myeloma also present with RI from other causes and it is important to determine their outcomes. Recent developments including the significant efficacy of proteasome inhibitor (PI) use in reversing renal failure, and the development of other new agents (such as monoclonal antibodies) are likely to improve disease outcome. The role of autologous stem cell transplantation (ASCT) in the transplantation-eligible (TE) population with RI has not been definitively established. Current International Myeloma Working Group (IMWG) guidelines indicate level C evidence for ASCT at a reduced melphalan conditioning dose of 140 mg/m2 ; however some studies have shown the feasibility and efficacy of full-dose conditioning,7,8 despite others recommending dose reduction in some patients.7,9 The choice of induction agent(s) in TE and non-TE patients also varies, and whether combination therapy provides incremental benefit in this high-risk group needs further clarification. With the overall improvement in prognosis in MM patients,10 it is crucial to evaluate whether there has been comparable progress in outcomes for this high-risk group with RI. In Australia and New Zealand, treatment protocols usually follow government reimbursement policy, for which combination novel therapies and maintenance therapy (other than thalidomide) are as yet unavailable outside of clinical trials. We investigated current treatment and clinical outcomes for MM patients with RI at diagnosis in Australia and New Zealand using a large, binational, real world, prospective clinical registry.

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