The Freelite© Chain Assay

Myeloma is not always easy to assess. In many cases, the usual types of tests don't reveal anything useful. For some of us, such as for me, the only laboratory test of value is the Freelite©, which measures the numbers of light chains in serum and calculates the ratio between the two.

I have no problem with the test except that patients often think the ratio has meaning.

Back in 1998, when I was diagnosed with multiple myeloma, there was an older test for light chains, but it wasn't usefully accurate. I took it regularly and charted its results, but doing so was more for curiosity than for practical application.

Every perfect plasma cell has attached to it two light chains. I find the pictures don't help a lot, but I'll add one (above). The light chains are called Bence-Jones proteins after being discovered many years ago by a doctor of that name.

Usually, a myeloma patient will find in his blood both types of light chains, with one abnormally high: kappa or lambda (don't get frightened by the mathematical-sounding names: they happen to be the initials of the people who discovered them, K and L). They tend to break off the plasma cell and circulate. The number of them in the blood is a rough measure of the infiltration of the bone marrow by myeloma. I think of the measurement as a poor-person's bone marrow biopsy: it's as close as we get to measuring something called "tumor burden" in other cancers. Some of us, like me, have no other way of measuring what the cancer is doing. Others, the true non-secreters, don't even have light chains and must rely on biopsies.

The problem with measuring light chains accurately is that they are stunningly small. Their weight is given in Daltons, which, if you didn't know, is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of 1.660538921(73)×10−27 kg. Light chains of type lambda are heavier (bigger) than of type kappa, which is why people whose type is lambda may have more kidney problems than kappas. The lambdas are more likely to clog the kidneys (drink lots of water).

A light chain is a VERY small thing.

Then two or three Australian scientists got an idea. After looking at the inaccuracy data of the old test, they thought they discovered two things. First, if the measurements of kappa and lambda were not correct, at least they were incorrect in the same way. That is, both measurements were either too high or too low, never one high and the other low. So they reasoned that if they calculated the ratio between the two types, the result would be accurate and wipe out the error. They even claimed the ratio to be predictive of future relapse. That's how we got the ratio: to compensate for defects in the original test.

By the time I got one of the authors on the phone, California to Australia, they had recanted on the ratio and its predictive value entirely. Ratio? What ratio? What it actually did was magnify the difference between kappa and lambda so that an observer wouldn't miss the drop in the non-dominant type, but that turned out to be relatively meaningless therapeutically. If you are type kappa, for example, it doesn't matter if the lambda drops and the ratio increases: treatment will be the same.

ARUP

Then we got the Freelite© test, which can accurately measure the light chains. In my case, the samples have to be sent to ARUP labs in Utah for analysis, so getting the results takes days, but at least the results are accurate, or, at least, have always made sense for me.

If you go to the Binding Site, who owns the test, here's what you'll find about the ratio:

"The serum free light chain ratio is a strong indicator of monoclonality and is valuable for distinguishing monoclonal from polyclonal diseases. "

Actually, the kappa and lambda measurements tell us that already.

Now to be fair, there are a few references to the ratio on the Binding Site, but if one looks further, one can find this from someone worth listening to, Sundar Jagannath:

"One third of patients with monoclonal gammopathy of undetermined significance have an abnormal free light chain ratio, and these patients harbor a greater risk of progression to plasma cell dyscrasia. For monitoring response to therapy, the international uniform response criteria define a normal free light chain ratio as an essential element of the "stringent complete response" category."

So, if you are MGUS, and the ratio moves but the k/l levels are still normal, perhaps it is the beginning of progression. I think. In any case, CR means a normal ratio in addition to normal levels of kappa and lambda, which, of course, a result we would expect.

Which, obviously, is more than I know about this subject.