Regarding kappa and lambda light chain values, which is more important to follow: the absolute values of each or the ratio?
It is the ratio of these two proteins that helps clinicians to get a picture of what is going on with your myeloma. Normally, kappa and lambda light chains make up part of antibodies that are produced by plasma cells and their absolute levels may naturally change (for example, in response to an infection or an autoimmune condition). In these circumstances, kappa and lambda blood test results will generally both go up or down in the same amount. Myeloma is a cancer of plasma cells, and patients with myeloma will show a higher level of either kappa or lambda light chains, depending on which type of cell clone (that is, either a kappa-producing plasma cell or lambda-producing plasma cell) developed the cancer. Because the level of one type of light chain will be higher, the ratio between them will be abnormal. For more information about M protein findings see our FAQ post here and view our High Impact Topic video on Learn Your Labs here.
Do you test for the expression of B-cell maturation antigen (BCMA) or other targets of bispecific antibodies?
No, clinicians do not check for expression of BCMA before prescribing a treatment that targets BCMA. The reason for this is that there are no data to suggest that BCMA expression is associated with better outcomes. For example, some patients with low BCMA expression respond well to treatment, and some patients with high BCMA expression do not respond to treatment. Researchers do not yet know what determines a treatment response to BCMA-targeted therapy. Currently, the only bispecific antibody approved to treat myeloma targets BCMA, therefore, no other targets are tested.
If someone has relapsed, how do you decide between CAR T-cell therapy or a bispecific antibody?
At the time of relapse, the first consideration in deciding the next treatment regimen is what treatment the patient received right before relapse and his or her overall health at the time. If the patient had an early relapse and, for example, had not yet received a monoclonal antibody as part of their treatment regimen, there remain a lot of treatment options. If the patient’s relapse occurs later, after, for example, 2 or more immunomodulatory drugs or 2 or more proteasome inhibitors, clinicians may look to treat with novel therapies such as bispecific antibodies or CAR T-cell therapy. However, access to these newer treatments may be limited to a cancer center that sees a lot of myeloma patients. Additionally, because of delays inherent in the manufacture of CAR T cells, some patients may not be able to wait (because their disease may be progressing) and that will impact treatment selection. For more information about CAR T-cell availability see our FAQ posts here and here and for more information on options for patients who relapse from CAR T-cell therapy see our FAQ post here.