Advances in Multiple Myeloma Diagnostic Work-up

Simon Murray, MD: Good afternoon. My name is Dr Simon Murray. I’m an internist from Princeton, New Jersey, and a clinical professor at Rutgers Robert Wood Johnson Medical School. I am joined today by Dr Ola Landgren, who is the chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, New York. Today we’re going to be discussing guideline-compliant testing for the early diagnosis of multiple myeloma and the roles of serum free light chain assays and serum protein electrophoresis. Good afternoon, Dr Landgren.

Ola Landgren, MD, PhD: Good afternoon, and thank you so much for having me.

Simon Murray, MD: I’m really excited to talk to you, because as internists we see cases of myeloma and often unfortunately, we mishandle them because they get diagnosed too late. What we’d like to find out today is ways that we can improve on, for general practitioners and internists, how we handle cases. I’ll start by telling you about a recent case I had. I have an 80-year-old patient who is a retired mail carrier. He has no medical problems other than mild hypertension. He was raised and lived in New Jersey his whole life. He’s African American, and he served in the Vietnam War. He presented to my office for a physical examination, which was entirely normal, but routine laboratory studies revealed a total protein level of 9 g/dL. Everything else was completely normal, including creatinine and CBC [complete blood count]. And I was concerned about the elevated protein. The next step that I took was to order serum protein electrophoresis, which came back positive for an M-spike [monoclonal protein]. The next step I took was to do an immunofixation test and a urine test for Bence Jones protein. Do you think, from your experience, that’s the appropriate way to have worked that up, to have approached that problem?

Ola Landgren, MD, PhD: I do think the work-up with a total protein being elevated triggers the thinking of looking if there could be a monoclonal protein hidden there versus if this could be a polyclonal elevation. This could be because of an inflammation or some more of a normal body response. That’s very important. So yes, the protein electrophoresis is what I would definitely do. In my practice, because I’m very specialized, I would not do it stepwise. I would do the protein electrophoresis. I will also do the immunofixation, and in addition to what you just mentioned, I would also do serum free light chain testing for kappa and for lambda. That would give me a lot of information. You mentioned the Bence Jones proteins, so historically that was discovered by Sir Henry Bence Jones in the United Kingdom many, many years ago. And that was discovered in the urine. I imagine I would look for light chains in the serum. Serum free light chain assets have been around for more than 15 years. I think they could replace the urine testing. We still do urine testing because we were trained to do that in medical school. Many times we do both urine testing and serum free light chain testing. There was 1 last detail here that’s clinically important, and I think the serum free light chain testing versus the urine testing a light chain are probably interchangeable. But the urine testing could also reveal if there is evidence of leakage of other proteins, so you would have to do a 24-hour urine test to rule that out. And, in the setting of plasma disorders, that would be to basically rule out that you don’t leak a lot of other proteins such as albumin, which could indicate that that could be AL [amyloid light-chain] amyloidosis. I would do a 24-hour urine. I would do serum free light chains. I would do protein electrophoresis and immunofixation to begin with. And if I establish that there were abnormal proteins from that point, I would not do anymore 24-hour urine tests. I would stop that. Then it will be serum-based light chain tracking.

Simon Murray, MD: I am presuming this man had no symptoms, no complaints. Would his diagnosis be multiple myeloma or would it be another diagnosis?

Ola Landgren, MD, PhD: Based on what we have talked about so far, that’s not possible to answer. The reason for that is because the definition for multiple myeloma in 2014 was changed from requiring basic symptoms to now also being a biomarker-defined disease. Specifically what that means is that the free light-chain kappa divided by lambda or lambda divided by kappa if the patient is a lambda secretor. If that ratio goes over 100, and assuming that the so-called involved light chain is 10 mg/dL or more, that would make it multiple myeloma, independent of symptoms.

Simon Murray, MD: Without symptoms, without crab—so-called crab symptoms.

Ola Landgren, MD, PhD: The protein markers we are talking about could make it a diagnosis of myeloma. There are 6 other variables, but that would be 1 of them.

Simon Murray, MD: That sounds to me like that test is a lot better than doing the urine test for benztropine protein.

Ola Landgren, MD, PhD: Well, the urine testing, as I mentioned, does not add really anything to the serum free light chain testing for the purpose of tracking light chains, and the diagnostic criteria are based on serum free light chain testing. But the urine 24-hour baseline test rules out that there’s no leaking kidney that leaks a lot of other proteins still could have a role. In reality the role is probably quite marginal for the urine testing.

Transcript edited for clarity.