Pee no more? Urine light chains down the drain

In this issue of Blood, Dejoie et al demonstrate the superiority of serum free light chain (sFLC) testing in the response measurement of light-chain multiple myeloma (MM) over urine in accuracy, sensitivity, and prognosis.¹ 

Light-chain production in MM occurs in nearly 80% of patients, with light-chain-only disease in 20%.²  The multiple ways in which myeloma can be monitored (serum M spike, urine M spike, sFLCs, urine light chains, and immunofixation) make the interpretation of results often complex if not even contradictory. Indeed, the correlation between each of these measures of disease burden is variable,³  especially in patients with renal insufficiency.

Of these tests, the least desirable has been 24-hour urine collection; it is inconvenient, can be difficult for patients, is prone to undercollection and overcollection, extends testing by at least an additional day, and has greater potential for inaccuracy than a blood test.⁴  Understandably, the use of sFLC testing has been preferred in the diagnosis and assessment of final response in patients with myeloma and is part of the International Myeloma Working Group’s updated criteria for the diagnosis of myeloma.⁵ 

Dejoie et al provide strong support for the preferential use of sFLC testing in the monitoring of patients with myeloma, at least in the subset that are light chain only. They demonstrate that serum testing of light chains is superior to urine in capturing patients with measurable disease, monitoring their response to therapy, and indeed in predicting their prognosis as evaluated by stringent complete response and survival. This has sweeping implications of reducing the need of urine testing and enhancing our ability to monitor patients accurately with this complex disease.

Their results do contradict certain previous studies, namely the Eastern Cooperative Oncology Group study by Dispenzieri et al in which the use of urine testing remained important in the monitoring of patients.⁶  However, those patients included all myeloma patients, not only those with light-chain-only disease. It is apparent that there remains no perfect test in myeloma as even serum light-chain levels are influenced by inflammation and renal dysfunction and can be inaccurately interpreted.⁷ 

Nonetheless, being less dependent on urine testing for monitoring of light-chain myeloma brings many advantages. More patients can be followed reliably and can therefore be eligible for clinical trials that they may not currently have access to. The ability to obtain more serial measures of the disease is desirable, especially in patients in whom urine collection may be difficult or impossible due to logistical reasons or oliguria. As light-chain myeloma itself conveys a worse prognosis due to its correlation to severe renal disease, providing more options to these patients is critical.

So have we come to a point where we can lose the dreaded urine collection bottle? Not so fast. Several situations will still necessitate us using them:

1. In the diagnostic workup of a patient with myeloma it remains important to fully assess disease and measure proteinuria.^8,9 

2. In patients with any suspicion of amyloidosis (or related diseases), 24-hour collections remain critical to assess for albuminuria.¹⁰ 

3. In patients with both heavy- and light-chain myeloma, it may be of value, especially when discordant results exist.⁶ 

It is likely that this trial will bring us closer to including sFLC testing in the monitoring of light-chain-only myeloma, but I suspect a further validation set will be required. It would also be of value to again confirm the cutoff values of 50% for response. Until that is achieved, however, beware of letting those urine light chains escape down the drain!