Pathophysiology and Diagnosis of Multiple Myeloma

Jatin Shah, MD: Multiple myeloma is one of the hematological illnesses that we see in addition to lymphomas and leukemias in Non-Hodgkin’s Lymphoma, as well as in Hodgkin’s Lymphoma. It’s lumped under hematologic malignances, but it is quite different than our leukemias and our lymphomas. Though it starts off in the bone marrow, it is a clonal proliferation of plasma cells. It’s very different in that sense because all of these hematologic malignancies start with a clonal proliferation of one of the bone marrow stem cells. In myeloma what you see is a clonal proliferation of plasma cells, and that’s how it’s very different than the other hematologic malignancies.

What you see with a clonal proliferation of plasma cells is you can see that with MGUS, or smoldering myeloma, but as that continues to progress and you see an increasing disease burden, you’ll start to see increasing end-organ damage or effect on the patient as well when we see these rising proliferation of plasma cells.

We see this typically in our older patients and so the average age is going to be in the 65 to 70 [year] range that we see in our patients with myeloma. Though we do see some younger patients in their 40s and 50s, this really is a disease of our older patients; patients above the age of 65 and 70 are the typical age that we’ll see, all the way going up to patients in their 70s and 80s.

There’s no clear reason for why patients develop myeloma, so there’s no clear risk factor—for example, smoking or alcohol intake or dietary intake. There are some risk factors that we can identify including radiation exposure and potential environmental exposures, benzenes and other carcinogens, but not a uniform criteria that we see. There’s not any other known genetic or hereditary risk factor that we can see as well for why patients may get myeloma as well.

When you look at the clonal proliferation of plasma cells in myeloma, oftentimes we can measure that with a paraprotein production that we see, including the serum paraprotein or the Bence Jones protein, which is, again, measuring these paraproteins that are made by these malignant plasma cells in the serum or the urine. So that becomes an important marker for your disease burden, and to see how the myeloma’s doing.

Importantly, when you start thinking beyond that, it’s really not that paraprotein that you worry about so much, but the effects of that on the patient. And so what we see in myeloma, which is different than what we see in other hematologic malignancies, or even different than other solid tumors, is really the effect on the end organs, and so there’s significant comorbidities that we see with myeloma. We can see an effect on the kidneys, and often these patients will come in with kidney failure at time of diagnosis or at later on, so they’re very prone to developing kidney failure.

Number two, they can also impact their bones. These patients will come in with significant osteopenia, lytic lesions, and impending fractures. Their bones become so weak that they have these things called pathologic fractures whereby lifting a gallon of milk or just lifting their arm, they can easily break their arm or legs. Or they’ll get compression fractures in their back, which can be very, very painful for patients as well. So, there’s significant comorbidities that we see. In addition to dealing with the cancer itself, we’ll see effects on the kidneys, and trying to deal with the kidney failure, or the bones. So patients have to get radiation or surgery, lots of pain medicines affecting their quality of life.

So what we see here is that it can affect the end organ in myeloma patients, both the kidneys as well as the bones. It’s also very immunosuppressive as well. So when you look at our myeloma patients, 25% of our myeloma patients are prone to getting infections being if they’re newly diagnosed or relapsed, regardless what line of therapy they on. So they’re prone to getting viral and bacterial infections, which we don’t see in other malignancies, so regardless of the chemotherapy, not due to immunosuppressive effects of chemotherapy, but due to the disease itself.

So, these patients come in with, for example, RSV, which is a common infection that we see in children, but rarely see in adults, but are immunocompromised myeloma patients, we tend to see RSV infections as well. Again, affecting the quality of life requiring hospitalizations, antibiotics or antiviral therapy. So I think that’s important, very different in myeloma compared to other tumor types, the significant impact on the patient’s quality of life that we’ll see an end-organ damage from the kidneys to the bones, to infections to hospitalizations to transfusion.