What is the difference between light chain myeloma and amyloidosis?

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Where does Al amyloidosis fall on the spectrum of plasma cell disorders?

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So that's a great question. And I think that's confusing to a lot of people because plasma cell because plasma cells range are really a spectrum of disorders that range from MGUS to symptomatic. Multiple myeloma. And if we start with symptomatic multiple myeloma, we realize that

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a patient with symptomatic myeloma not only has a high burden of plasma cell disease in the bone marrow and circulate and with an abnormal protein in their blood or urine, but they also have end organ damage attributable to those plasma cells or the protein they have bone lesions, destructive bone lesions or anemia or kidney disorder, kidney dysfunction or

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immune problems related to the plasma cell disorder. And that's called symptomatic myeloma

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And those patients usually have greater than 10% plasma cells in their bone marrow. And again,

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the organ damage attributable to the myeloma. On the other end of the spectrum is MGUS, which there's a low burden of plasma cell disease and no organ damage attributable to the plasma cell disorder.

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And those patients have less than 10% plasma cells in their bone marrow. They have a low burden of circulating protein in their blood or urine, and clinically they are fine. In the middle is something called asymptomatic myeloma, where the patients have greater than 10% plasma cells but no organ damage. And we call those patients asymptomatic myeloma. Although we're studying new treatments for them.

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The standard of care has been to monitor these patients because over time, there's a some of those patients will not develop symptomatic disease. And as you know, myeloma remains incurable to date, however. So where does amyloid fall on this on the spectrum? In 60% of patients with amyloidosis,

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there's less than 10% plasma cells in the bone marrow. And these so they fall in the MGUS category.

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However, if they have end organ damage attributable to the misfolded protein and such as heart failure or kidney problems related to the amyloid amyloidogenic protein in that tissue, this patient doesn't have MGUS plus amyloid. This patient has primary systemic amyloidosis. So in 60% of the patients with amyloid, they have less than 10% plasma cells in their bone marrow.

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However, about 40% will have greater than 10% plasma cells in their bone marrow, as well as the characteristic end organ damage attributable to the amyloid protein. Those patients also they don't have asymptomatic myeloma. If all of the end organ damage is attributable to the amyloid protein, those patients also have

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primary systemic amyloidosis. At times we we classify them as having myeloma because for insurance purposes and things like that, the drugs that we use for multiple myeloma often

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we can use for amyloid.

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But unfortunately in the year 2019, there's still not one FDA approved drug for this condition. So that if we designate them as having myeloma, we can have more access to drugs.

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In 2021, the FDA granted accelerated approval to Darzalex Faspro in combination with bortezomib, cyclophosphamide, and dexamethasone for

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al amyloidosis.

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the pathophysiology of the two diseases are distinct.

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so that I think it's important to recognize if all of the patients path flow physiology is attributable to the amyloid protein, despite having greater than 10% plasma cells in their bone marrow, they have primary systemic amyloidosis.

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There is ten about 10% of patients who actually have and organ damage attributable to myeloma, meaning bone lesions, anemia, kidney, tubular damage from myeloma proteins

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and have at the same time amyloid affecting their organs. And those patients have true true amyloid and multiple myeloma