There is so much information being produced and shared at the American Society of Hematology (ASH) Annual Meeting, it is challenging to digest it all and distill it down. In review of the many screen shots I took of the presentation slides, one piece of information that becomes granular is that there is not “one” myeloma, it is truly a heterogenous disease captured under one umbrella. I will try to break down a few versions:
Heavy chain: the clonal immunoglobulin can be IgG, IgA, IgM, IgD or IgE
Light chain: this can be of kappa or lambda subtype
Most people with myeloma have one of each, for example, IgG Kappa. However, there are some people who have just a light chain-derived disease, kappa or lambda. And to add to the confusion, some people have neither, although much less common, and are considered non-secretory. So, if a person doesn’t have a heavy or light chain, how is the myeloma found? That is where we get more granular with the information being learned.
First, we need to look at myeloma defining events (MDE) known as SLiM CRAB which stands for Sixty percent (or more) plasma cells (PC) in the bone marrow; Light chain ratio >100 (although doesn’t apply in non-secretory disease); MRI-defined lesions, at least 2, >5 mm; Calcium elevation, Renal dysfunction, Anemia, Bone disease.
It is really with the CRAB portion of MDE that will lead to a diagnosis of non-secretory myeloma. A person may present with severe fatigue from anemia or pain from a non-traumatic bone fracture. Sensitive imaging techniques like MRI, PET or CT may show bone or soft tissue tumors known at plasmacytoma (tumor made of plasma cells). Extra-medullary disease (EMD) (disease outside of the bone marrow) can present in this way, or within an organ, and is also a less common variant of myeloma. Plasma Cell Leukemia, now defined as having at least 5% circulating plasma cells, also falls into the less common variant of myeloma.
In this short space, we can count at least 15 subtypes of myeloma and we have not even touched on risk stratification based on cytogenetic abnormalities (CA). When a bone marrow or tissue biopsy is taken, the genetic make-up of the myeloma cells can reveal changes that identify “Standard” versus “High” risk variants. High risk CA have been identified as t(4;14), t(14;16) & del(17p). CA of chromosome 1 (1q+, 1p-) are associated with intermediate to high-risk disease activity. Then, to add to the complexity, standard risk genetics may be seen, but the myeloma is acting like high risk, therefore, considered “functional” high risk.
For those people having more than 1 HR feature, terms such as “double hit”, “triple hit” and “ultra” high risk have been used. Dr. Timothy Schmidt, MD, Assistant Professor of Medicine from University of Wisconsin – Carbone Cancer Center, really outlined this information at the December 10, 2022, education session, “Multiple Myeloma – Assessing the Patient and the Disease” and his talk “High or Low? Assessing Disease Risk in Multiple Myeloma.” Risk status needs to be assessed at time of diagnosis and over time as the disease can change over time. The reason to assess disease risk is to guide approach to therapy. There are clinical trials directing attention to ultra HR disease (BMT CTN 1902, MASTER2) to better understand how to treat this challenging myeloma variant. Slides from his talk are captured in my Twitter feed from that date.
What I have been sharing so far are “disease” factors that contribute to the diagnosis and the treatment plan. We have not talked about the “person” factors, which is integral to the discussion as we are treating a person, not just a disease. There were a lot of sessions about Fit versus Frail, geriatric assessment and how to tailor therapy in the frail/elder person. Since the average age of diagnosis is 70 years old with >50% of people have co-morbidities, Fit/Frail assessment is necessary when creating a plan of care. Ciara Freeman, MSc, FRCPath, MBBChir, MRCP, in the same education session, emphasized the need for practitioners to take the time to assess frailty, making sure that increased age was not the definition of frailty, and that frailty is dynamic and needs to be re-assessed over time. Slides from her talk are captured in my Twitter feed from that date.
There are so many factors when it comes to assessing and treating a person with myeloma. And let’s be clear, we are treating a person with myeloma, not myeloma. We can never lose sight of a person’s goals and preferences when discussing treatment options. Ultimately, we want durable and deep responses to therapy while keeping in mind quality of life and minimizing toxicity. In my next blog, I will highlight some of the newer therapies that are being evaluated in myeloma and what some of the toxicities are to watch for.
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Teresa Miceli, RN BSN OCN
SGL Nurse Liaison
IMF Nurse Leadership Board
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