September 30, 2023
September 30, 2023

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It is not often that you can say that the best place to seek care for a certain cancer is in Arkansas. Most of what we know about multiple myeloma comes from decades of careful and painstaking research conducted at the Mayo Clinic in Minnesota. But then there is Bart Barlogie, MD.

Barlogie was born in Germany in 1945, went to medical school at the University of Heidelberg, and did his residency at the University of Munich. In 1974, Emil Freirich, a leukemia expert from MD Anderson Cancer Center, visited Munich and met Barlogie and invited him for a fellowship to MD Anderson, where he began his myeloma research. Lucky for Barlogie, in 1989, Sam Walton of Walmart fame came to MD Anderson for treatment of his myeloma. Walton was impressed by Barlogie; as a result, he pulled up stakes to move to the University of Arkansas in Little Rock, where he started the Myeloma Institute where Walton subsequently received his own treatment. From then until he moved to Mount Sinai in New York in 2015, Barlogie treated over 11,000 myeloma patients.

The key cells in the immune system are lymphocytes, which are subdivided into B cells and T cells. B cells are the cells that react to toxins by producing antibodies; the final cell in that pathway is the plasma cell. The plasma cell is the B cell which actually produces proteins, known as antibodies or immunoglobulins, in response to antigens, foreign substances that the body recognizes as “other” and to which it mounts a defensive reaction.

Any of these cells can become malignant. When B or T cells become malignant, we are confronted by lymphomas or leukemias. When a plasma cell becomes malignant, the cancer that develops is called multiple myeloma. Typically, this is a malignancy of a single clone of plasma cells, i.e., a plasma cell that is producing an antibody to a single specific antigen; almost always this antigen is unknown. Therefore, when we identify such a case, aside from finding high concentrations of plasma cells in the bone marrow, a patient with multiple myeloma will also demonstrate a spike on his serum protein electrophoresis (SPEP). The SPEP shows the antibodies in the serum. Normally, we all have many antibodies in our blood to all sorts of antigens, reflecting all the exposures we have had during our lives, and thus there is a broad band of antibodies present on the SPEP, but in the patient with myeloma there will be a “spike” or peak protruding from the band, reflecting the single antibody that is being hyper-produced due to the malignant plasma cell. This is typically how we recognize the presence of myeloma and monitor its clinical course.

Plasma cells produce a variety of immunoglobulins so the M-proteins can likewise be a variety of immunoglobulins—IgG, IgA, IgD, IgE, IgM. In addition to a monoclonal spike or M-spike, multiple myeloma is characterized by an excess of plasma cells in the bone marrow, so a bone marrow biopsy is typically part of the work-up, along with a skeletal evaluation. Myeloma cells can concentrate in bone and cause lytic (destructive) bone lesions—this is a common and classic characteristic of myeloma. These bone lesions are called myeloma and give the disease its name—patients typically have weakened bone as in osteoporosis and thus are prone to fractures and spinal collapse. The lytic lesions can be very painful, which is one symptom of myeloma. The bone destruction also leads to the release of calcium from bone, so hypercalcemia is another classic problem associated with myeloma. The excessive immunoglobulins can also overwhelm the kidney and damage the glomeruli, leading to renal failure. In medicine, we like acronyms; the acronym associated with myeloma is CalciumRenalAnemiaBone—CRAB.

If you are getting the sense that this can be a very unpleasant disease, you are quite right. It is generally a disease of the elderly and, similar to prostate cancer, is dramatically more common in those of African origin.

Multiple myeloma is incurable. In the past, it had a survival rate that ran to about two years. However, dramatic improvements in treatment have occurred over the past 25 years that include more effective chemotherapeutic agents, in conjunction with autologous bone marrow transplantation. These treatments have given extended life to most patients; 10- and 12-year survivors are now common, and with excellent quality of life.

Most dramatic of all, a treatment modality known as CAR-T cell therapy was recently introduced and shown to be highly effective in extending survival. We have not yet seen the full effects of this therapy on outcomes for multiple myeloma.

Multiple myeloma is an inordinately complex disease, with a constellation of symptoms and complications stemming from the problems described above. The interplay of excess immunoglobulins, bone manifestations, metabolic problems and hematologic complications can be daunting to unravel for any given patient, and the treatment options nowadays are multiplex as well. The complexity of this particular tumor mandates the use of second opinions and use of as sophisticated a cancer center as you feel comfortable with. This returns us to Bart Barlogie. In Arkansas, he introduced highly aggressive therapies, including tandem stem cell transplants (two in a row) and the use of thalidomide (now a standard drug). He achieved survival rates that were so long that some believed that he had almost achieved cures.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

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