Case Presentation
Mrs. Jane Smith arrives in the office complaining of severe fatigue and back pain. She is a 60-year-old female, married with two grown children. For the last six months she has been noticing progressive fatigue toward the end of the day, to the point that over the last four weeks she has cancelled her exercise class or left early due to shortness of breath. On review of her systems her main complaint is mild to moderate lower back pain. Her past medical history is unremarkable and she is on no medications except multivitamins. On physical exam, her vital signs are normal, she has moderate skin pallor, and her cardiopulmonary, abdominal, and neurological exams are unremarkable.
Laboratory examination is remarkable for a hemoglobin of 9gm/dL, a total protein of 11gm/dL and a creatinine of 2.0mg/dL. Further testing includes a serum protein electrophoresis, which reveals IgG kappa peak of 6.5gm/dL, beta-2 microglobulin of 3.0, bone marrow aspirate reveals 60% plasma cells, and biopsy reveals sheets of clonal plasma cells. Cytogenetics of the bone marrow aspirate reports no cytogenetic abnormalities. Radiologic evaluation reveals multiple small lytic lesions throughout the skull and weight-bearing bones. MRI of the axial skeleton reports diffuse marrow infiltrative disease.
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Optimal Induction Therapy for Multiple Myeloma
The above case illustrates a classic presentation of a patient with multiple myeloma.1 The patient has symptomatic disease as documented by progressive anemia with a decrease in exercise tolerance and increased fatigue. Patients with symptomatic multiple myeloma require treatment to prevent further organ deterioration and to provide symptomatic relief. Effective therapy that results in objective responses as defined by the International Myeloma Working Group Criteria (IMWG) not only produces symptomatic benefit but also improves outcomes.2
Optimal induction for patients with multiple myeloma requires a thorough history and physical examination to determine the right choice and timing of therapeutic agents. Table 1 summarizes the characteristics of optimal induction therapy.
Table 1. Characteristics of an Optimal Induction Therapy for Multiple Myeloma3
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HISTORICAL PERSPECTIVE |
MODERN PERSPECTIVE |
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High response rates |
Melphalan and prednisone combination has an overall response rate (partial response or greater) of 50%. The combination of vincristine, adriamycin and pulse dexamethasone (VAD) has a response rate of 60% to 70%.Thalidomide based therapies associated with 70% response rates and better than VAD in randomized trials. |
Lenalidomide, bortezomib, dexamethasone combinations associated with response rates of +90% with 30% of patients achieving a complete remission |
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Well tolerated |
Melphalan and prednisone combination is well tolerated. Prolonged exposure to melphalan is associated with an increasing risk of secondary leukemias and myelodysplasia. VAD requires an intravenous catheter for the infusion of the doxorubicin; pulse dexamethasone has significant side effects (hyperglycemia, mood changes, infections); prolonged vincristine exposure is associated with peripheral neuropathy. Thalidomide induction is associated with neuropathy in more than 50% of patients. Deep venous thrombosis and neurocognitive side effects results in 30% of patients discontinuing therapy. |
Severe neuropathy occurs in 5% to 10% of patients with bortezomib-based inductions. Risks are reduced if bortezomib is given on a weekly schedule and/or subcutaneously. Lenalidomide is associated with cytopenias and deep vein thrombosis. |
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Preserves stem |
Prolonged melphalan exposure impairs stem cell mobilization and collection. |
Prolonged lenalidomide exposure can affect stem cell collections if mobilized with filgrastim alone. Chemo mobilization of plerixafor mobilization usually successful. |
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Easy to administer |
Melphalan and prednisone combination is orally administered; no adjustment for renal function required. No adjustment for renal function required VAD. |
Lenalidomide, bortezomib, dexamethasone are well tolerated |
