Blood cancers

Poor survival in light chain myeloma may be addressed by preventing renal damage


The poor survival rates of patients with light chain–predominant multiple myeloma are driven by renal injury that may be ameliorated by plasmapheresis and dialysis, US researchers say.

In a series of investigations, clinicians at Augusta University, Georgia have shown that the light chain–predominant subgroup comprising  20% of patients with multiple myeloma have higher rates of kidney dialysis and clear signs of kidney injury such as hypertension and proteinuria.

And in their new study they conclude that the higher death rate and shorter survival in “light chain myeloma’ patients may be attributed to greater disease burden in the form of excess serum free light chains that compromise renal function

Published in Laboratory Medicine, their study compared data from 316 patients with conventional and 71 patients with light chain–predominant multiple myelomas with secretion of intact immunoglobulins.

Laboratory and clinical findings for the two groups showed that patients with light chain–predominant multiple myeloma had a significantly higher death rate (35% vs 14%) compared to the conventional group.

The comparison also showed a higher rate of chronic dialysis (18% vs 4%), a lower estimated glomerular filtration rate (46 vs 69 mL) and serum albumin (3.44 vs 3.7 g/dL), a significantly higher urine protein concentration (239 vs 76 mg/dL), and a significantly higher prevalence of hypertension (87% vs 72%) and blood transfusion requirements (83% vs 71%).

The differences were all indicative of more severe renal pathology in light chain–predominant multiple myeloma patients, and the greater extent of renal failure can also explain the higher frequency of blood transfusions in these patients, the study authors said.

“The shorter survival of patients with light chain–predominant multiple myeloma is clearly associated with renal damage caused by excess free immunoglobulin light chains.

“Excess free immunoglobulin light chains are a known risk factor for renal disease, with light chain cast nephropathy being the usual pathogenetic mechanism for renal damage,” they wrote.

“Addressing the free light chain burden early in the course of illness in [these] patients may have the potential to mitigate or reverse renal pathology,” they added.

Lead investigator Dr Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology at the Medical College of Georgia at Augusta University said renal damage may be ameliorated by early aggressive treatment with chemotherapy, plasmapheresis, and dialysis.

Tests can be done to identify these individuals by measuring free light chains, but there are currently no targeted treatments when they are identified, which is why clinical trials are needed, Dr Singh said.

“Prospective controlled trials designed to aggressively lower serum free light chain concentrations to improve outcomes are warranted,” he wrote.

In healthy individuals, these excess light chains are simply filtered out by the kidneys and eliminated in the urine, but in light chain multiple myeloma, “Everything is multiplied, the kidneys get bombarded and the tubules get clogged,” he said. You can see the protein deposits in a biopsy, he added.

 

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