Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published September 20, 2023


What three-drug regimen is commonly used in the United States to treat multiple myeloma?

A defining feature of plasma cell disorders is a clonal proliferation of plasma cells that produce monoclonal immunoglobulin or light chains that can be detected in the blood or urine. Read the NEJM Case Records of the Massachusetts Hospital here.

Clinical Pearls

Q: Name some common and uncommon plasma cell disorders.

A: Plasma cell disorders range from asymptomatic conditions, such as monoclonal gammopathy of undetermined significance (which is present in >3% of persons >50 years of age) and smoldering multiple myeloma, to symptomatic conditions, such as multiple myeloma and solitary plasmacytoma. Less common plasma cell disorders include AL amyloidosis and even rarer entities, such as monoclonal gammopathy of renal significance and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes).

Q: What are some of the features of multiple myeloma?

A: The median age among persons with a new diagnosis of multiple myeloma is 69 years, and only 3.2% of cases of multiple myeloma are diagnosed in persons younger than 45 years of age. Extramedullary disease, which is disease outside the bone marrow, is present in only 6% of patients with a new diagnosis. Spontaneous tumor lysis syndrome is uncommon in patients with multiple myeloma.

Morning Report Questions

Q: What are the updated criteria for the diagnosis of multiple myeloma?

A: Criteria for establishing the diagnosis of multiple myeloma are unique, in that either pathological or clinical findings indicative of end-organ involvement are required. Multiple myeloma was traditionally defined by the presence of one or more of the four “CRAB” criteria: hypercalcemia, renal impairment, anemia, and bone involvement. In 2014, the criteria were updated to include myeloma-defining biomarkers that could identify patients who are at high risk for the development of traditionally symptomatic disease: a ratio of involved free light chains to uninvolved free light chains of 100 or greater, bone marrow involvement (with clonal plasma cells involving ≥60% of bone marrow), or the detection of more than one focal lesion on magnetic resonance imaging.

Q: What three-drug regimen is commonly used in the United States to treat multiple myeloma?

A: Treatment for multiple myeloma has evolved considerably in the past two decades. Before the 2000s, the main strategy for achieving a deep response was the administration of high-dose melphalan and autologous stem-cell transplantation. The introduction of several pivotal drug classes — proteasome inhibitors (e.g., bortezomib, carfilzomib, and ixazomib), immunomodulatory drugs (e.g., thalidomide, lenalidomide, and pomalidomide), and anti-CD38 monoclonal antibodies (daratumumab and isatuximab) — has transformed the treatment options, leading to improvements in quality of life and overall survival. These drugs are effective when administered in combinations, and they can be used in patients who are older and frailer. A three-drug regimen — lenalidomide, bortezomib, and dexamethasone — is commonly used in the United States. The anti-CD38 monoclonal antibody daratumumab is increasingly being added to this three-drug regimen for the treatment of patients with newly diagnosed multiple myeloma who are eligible for intensive treatment.

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