Dr Richter on Early Abnormalities Indicative of a Multiple Myeloma Diagnosis

"Anytime we see the CRAB symptoms—high calcium, kidney problems, anemia, or bone lesions—myeloma should be part of that diagnostic process. [Additionally, many clinicians] will only consider multiple myeloma or monoclonal gammopathy of undetermined significance [during diagnosis]. There is a lot of middle ground of plasma cell problems that are not myeloma but also not monoclonal gammopathy of undetermined significance…such as light chain amyloidosis."

Joshua Richter, MD, an associate professor of medicine in the Division of Hematology and Medical Oncology at The Tisch Cancer Institute, as well as the director of Multiple Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai, discussed clinical presentations and laboratory findings that could aid in the identification of early abnormalities suggestive of multiple myeloma.

Early recognition of plasma cell disorders, including multiple myeloma, requires vigilance for clinical and laboratory abnormalities that may initially appear nonspecific, Richter began. Hallmark features, such as hypercalcemia, renal dysfunction, anemia, and bone lesions—collectively referred to as CRAB symptoms—should prompt an evaluation for underlying plasma cell dyscrasia, he detailed. For example, anemia with preserved iron stores or unexplained hypercalcemia warrants assessment for a monoclonal gammopathy, he explained. Serum and urine protein electrophoresis with immunofixation, as well as serum free light chain assays, are key initial tests in such cases, Richter said. He advised clinicians not to dismiss subtle abnormalities in these parameters, as they may signal an underlying clonal process.

It is also important to recognize that plasma cell disorders exist on a spectrum, Richter continued. Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma are commonly considered, intermediate conditions, such as systemic light chain amyloidosis, are frequently overlooked, Richter stated, noting that patients with these entities may present with low-level monoclonal protein spikes that still carry clinical significance. For example, a monoclonal spike of 0.2 g/dL may be associated with significant organ damage, such as that seen in amyloidosis, whereas a higher spike (e.g., 3.5 g/dL) may indicate smoldering multiple myeloma that does not yet warrant treatment, Richter explained. Diagnosis should therefore be guided by clinical context rather than protein quantity alone, and small monoclonal spikes should not be assumed benign without further investigation, he concluded.