Prof Meletios Dimopoulos talks to ecancertv at IMW 2013.
Renal impairment is a common complication in multiple myeloma (MM). It is seen in 20-40% of patients with MM. In about 5% of cases, acute renal impairment occurs, which is oliguric and may require haemodialysis.
The reason for this is the production of free light chains in excess to heavy light chains by myeloma cells. These filter through the glomeruli and accumulate in the renal tubules. In some patients cast formation occurs and these can obstruct the renal tubules, leading to deterioration of renal function.
Outside of MM itself, a number of risk factors predispose patients to renal impairment. In around of 10% of patients there is hypercalcaemia, which is a cause of renal impairment. In addition, many patients complain of bone pain prior to diagnosis of MM, which has been treated with nonsteroidal anti-inflammatory drugs.
These agents predispose to renal impairment as well. Furthermore, these patients are often dehydrated, which contributes to renal impairment. Finally, antibiotics used for the treatment of infection and contrasting agents used in imaging are both nephrotoxic.
Renal impairment significantly impacts on prognosis and overall survival in MM patients. It is the most common cause of early mortality in MM patients, with death seen in the first 2 months from diagnosis. It also causes significant morbidity and increases the expense of treating these patients. Before the era of novel agents, renal impairment prevented MM patients from receiving appropriate therapy.
Supportive care is provided to these patients in the form of haemodialysis for oliguric patients. Rehydration is also very important and to avoid procedures that may aggravate renal impairment.
Some mechanical procedures have also be used, including plasma exchange, but have not been very successful. This is because the light chains have a low molecular weight and are not effectively removed with this procedure. Today, however, there are some special haemodialysis filters with large pores that are able to retain the free light chains.
The advent of novel therapies has significantly impacted on the treatment of MM with renal impairment. In combination with high dose steroid therapy, bortezomib is the mainstay of therapy and has been shown to be safe and effective in these patients. In fit patients, a third agent can be added, include cyclophosphamide, doxorubicin or thalidomide. Lenalidomide can be considered with a dose adjustment.
High dose therapy and autologous stem cell transplant (ASCT) has been used in these patients, with a dose adjustment of melphalan. However, with the use of novel agents, the use of high dose therapy in these patients is decreasing.
Carfilzomib can be given to renal patients with no impact on renal function. Pomalidomide can also be used safely in patients with a creatinine clearance above 45 mL/min. However, there are ongoing studies to evaluate the use of pomalidomide in patients with lower creatinine clearance.
This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).