What is macro focal myeloma? How is it diagnosed?

What is macrophocal myeloma and how is it defined? So macrophocal myeloma is another very undefined area. The imaging modalities that we started doing, like the MRIs and the PET scan, started to find a disease pattern that has not been defined before, which is a patient that has very few plasma cells in the bone marrow or no plasma cells in the bone marrow and tumors scattered throughout the skeleton usually formed of plasma cells, what's called plasmascytoma. They are usually more than one and that's why it's called multifocal. If it's only one it's called solitary plasmascytoma and that's a completely different entity. But the multifocal plasmascytoma is a scattered lesions or tumors throughout the skeleton made of plasma cells. They usually don't secrete a lot of protein and they are actually quite difficult to diagnose. Patients usually present with pain and fractures and then you do a biopsy and you find the plasma cells. Most of those patients present with pain and usually it's diagnosed in younger patients, so especially in newly diagnosed patients, usually younger patients, and the outcome of those patients is quite good. We treat them with systemic treatment, we give them systemic treatment and stem cell transplant if they meet the criteria for that, followed by maintenance and they have excellent outcome. That's when it occurs upfront or newly diagnosed. The multifocal plasmascytoma that occurs later on in the disease is a little bit of a different entity and it is being seen more nowadays. So we see a lot of those multifocal elapses occurring in myeloma with bone marrow showing no plasma cells but tumors popping up usually in the shoulders or back. This particular entity is being seen nowadays in immune therapy. So now with patients that have allogeneic transplant, for example, when they relapse, their bone marrow is completely taken over by the donor cells and the relapse occurs outside of the bone marrow in those multifocal sites. The same with some of the CAR T cell trials. Most of the CAR T cell trials clean up the bone marrow very quickly. You have what's called MRD negativity, the bone marrow is clean, but you still have some of those focal areas. In general, the multifocal plasmascytoma that occurs in the relapse setting do have a poor outcome and those patients do not do as well as those who present upfront with multifocal plasmascytoma. How are multifocal plasmascytomas treated in the relapse setting? In relapse you try different things. You try as you try any relapse disease. If it's causing a lot of symptoms at diagnosis or in relapse, then radiation might be indicated. If radiation is not indicated, then you use systemic treatment and it follows the same paradigm you do for any relapsed myeloma. Why do plasmascytomas often appear in heavily pre-treated myeloma? In general, normal plasma cells secrete more or less the same amount of heavy chain and light chain and that's how you have the immunoglobulin molecule. When your disease starts progressing, you start secreting more light chains and that's how you pick up the benjamins protein in the urine or the free light chain in the serum. As the disease becomes more aggressive, some of those cells stop making light chains and heavy chains and they become lymphoma-like disease and those patients form tumors and this can be tumors in the soft tissue or in the bones. So there is really no clear distinction between what represents early myeloma versus late myeloma. This kind of plasmascytomas can be present in multiple stages of the disease.