What should individuals diagnosed with MGUS and smoldering multiple myeloma know about amyloidosis?
When it comes to amyloidosis, myeloma patients are at risk, as I've mentioned. However, these patients are generally being treated for their myeloma and good treatment for myeloma is the best thing you can do for AL amyloidosis. A group at particularly high risk are patients with pre-multiple myeloma that are not on treatment, namely MGUS and smoldering myeloma, because patients with MGUS and smoldering myeloma are generally observed and not treated. And if their abnormal protein conform amyloid, they can slowly start to get sick while not being treated at all. So that's definitely a group of patients that we focus on very carefully. And when we see them regularly, I'm not only asking them questions about how they feel with the myeloma perspective in mind, any new bone pain, for example. I'm also asking them questions about shortness of breath and weight loss and more bubbles in their urine when they urinate, a sign of proteinuria because these are some signs that amyloid could be developing. So the MGUS and smoldering population, we need to pay careful attention to them because they can certainly develop amyloidosis. And if they do, we would want to jump on their disease and treat them. No more observation because their abnormal blood disease, their abnormal proteins are hurting them and in that case they must be treated.
Why is it a good idea for a person diagnosed with smoldering multiple myeloma or MGUS to be followed by a myeloma specialist?
When it comes to MGUS and smoldering myeloma, it's true that patients don't require treatment and they're observed. However, observation does require a degree of expertise. You need to know what you're observing for. Certainly, increases in the myeloma proteins in the blood are fairly obvious to see, but subtle clues like someone who's not feeling well, getting sicker, that may be confused for other issues. They're going to see their cardiologist. They're going to see their primary care doctor. And no one's paying attention to the smoldering myeloma because that doesn't hurt people. Well, that person needs some expertise associated with their case. A myeloma expert, I think, can be very helpful there because myeloma experts see all of the complications of these diseases, even the more rare ones like amyloidosis and can intervene before people are too sick. Dr. Comenzo at Tufts is conducting a trial. It's called the SAVE Trial. The SAVE trial stands for seeking amyloid diagnosis very early because the biggest problem is if we don't recognize these patients, they present with advanced organ failure. In that trial, patients who present with MGUS and a Lambda light chain or asymptomatic myeloma and a lambda light chain with an abnormal free light chain ratio. We are screening those patients to see if they produce an amyloid genic light chain. Distinct from multiple myeloma, where Kappa is the more common isotype that the plasma cells produce. In amyloid, it's the lambda light chain then predominates. So in patients who have asymptomatic myeloma or MGUS and have a lambda light chain with an abnormal free light chain ratio, we are requesting a blood sample to be sent to Dr. Comenzo’s lab where he can type the light chain and determine if it is indeed an amyloid genic chain based on previous work.
What are some symptoms of amyloidosis that a smoldering myeloma patient should be aware of?
Patients with amyloid tend to feel very unwell. They are tired, they're short of breath. They mimic conditions like heart failure. They have swelling in their legs. They can have just upset stomach or no appetite. They can have diarrhea, they can have blood in their stool varying, but it's very non-specific and sometimes they can just feel unwell and most of the time they go to multiple specialists to try to understand what is causing their symptoms. But if you don't recognize that this is amyloidosis then or even think about amyloidosis, then it goes undiagnosed because they say, oh, you don't have any or if you have multiple myeloma, but no kidney failure or bone lesions or anemia, or immune problems, the doctor will say, oh, you have asymptomatic myeloma, but doesn't recognize that fatigue, shortness of breath, lower extremity edema or problems like that can be attributed to amyloid as the result of the underlying plasma cell disorder. They often present more to the cardiologists who sometimes send them to a pulmonologist because their heart failure is not typical heart failure. It's right-sided heart failure instead of left-sided heart failure. And actually, in a survey that we did of 443 patients and caregivers, we found that the average number of physicians that an amyloid patient goes to before they get a confirmed diagnosis is four, and 80% of patients go undiagnosed for over a year.