Myeloma and AL Amyloidosis are plasma cell diseases. Plasma cells are normally cells that produce immunoglobulins, the antibodies that help fight infections and support our immune systems. Plasma cell diseases are a type of blood cancer in which plasma cells become malignant and can cause damage to the bones, kidneys, heart, bone marrow and immune system, and as a result can make patients sick. Plasma cell diseases include multiple myeloma, systemic light-chain (AL) amyloidosis, and monoclonal immunoglobulin deposition disease. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma are plasma cell diseases in which patients are not yet sick because they have very limited organ damage, if any.
Identifying plasma cell diseases
The hallmark of plasma cell diseases is the measurement in the blood and urine of antibody proteins produced by the malignant plasma cells; in each patient these cells produce an identifiable immunoglobulin signature, usually an intact immunoglobulin with a ‘heavy chain’ such as immunoglobulin G or A (IgG or IgA) and a ‘light chain’, either kappa or lambda (κ or λ). In 20% of patients with myeloma and the majority of patients with AL amyloidosis only the κ or λ light chain is produced. We often refer to these proteins as the M-spike. We follow these signature proteins during therapy because as the number of malignant cells decreases, these proteins decrease as well, showing that the patient is responding to treatment.
Tracking your body’s response to treatment
When we can no longer identify these signature proteins in a patient, a complete response has usually been achieved. A complete response is not a cure. Most patients eventually relapse and require more therapy, often 4 to 5 years after their initial diagnosis and treatment.
Relapse occurs because patients still have a very small amount of remaining disease, what we call minimal residual disease, even after we cannot find the signature proteins in the blood or urine. We now have clinical research tests for minimal residual disease that can help define the risk of relapse in each patient. The genetics of the plasma cell disease and the depth of the complete response can be assessed by determining the presence of minimal residual disease. The presence or absence of minimal residual disease would determine how long the response is maintained in individual patients. The genes of the plasma cell disease and the amount or burden of the plasma cell disease at diagnosis are major factors that determine how long the complete response can be maintained.
Although much work still needs to be done, our treatments and our understanding of plasma cell diseases have advanced significantly in the past two decades as the result of focused clinical studies, comparative analyses of patient outcomes, and translational research studying the malignant plasma cells from patient bone marrows.
The importance of finding and treating plasma diseases quickly
While patients most often experience injury to the kidneys, bone and bone marrow from plasma cell diseases, patients can experience heart damage at diagnosis or at relapse. At diagnosis, patients with AL amyloidosis and heart damage need to be treated promptly and effectively, and at relapse patients with recurrent heart damage or with relapsed myeloma and new heart damage need to be diagnosed and treated quickly as well. The damage is often reversible, but in some patients it may be so advanced that aggressive cardiology interventions, including heart transplantation, may be needed.
Similarly, bone or kidney damage can be reversed if caught early; in a small number of patients orthopedic interventions such as hip replacement may be needed. The principle that applies in all plasma cell diseases is that early diagnosis and treatment can control the plasma cell disease and reverse organ damage, thereby restoring a patient’s quality of life and normal level of activity.