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KEY CONCEPTS

KEY CONCEPTS

  • Image not available. Multiple myeloma (MM) is a cancer that develops in plasma cells, leading to excessive production of a monoclonal immunoglobulin.

  • Image not available. Most patients have skeletal involvement at the time of diagnosis with associated bone pain and fractures. Anemia, hypercalcemia, and renal failure may also be present. A bone marrow biopsy with 10% or more plasma cells and a M-protein spike on plasma or urine electrophoresis confirms the diagnosis.

  • Image not available. Cytogenetics may play an important role when selecting the appropriate initial therapy for patients with a new MM diagnosis and tools such as the Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART) approach are available.

  • Image not available. Induction treatment is based on patients’ eligibility for autologous stem cell transplantation. Novel agents such as thalidomide, lenalidomide, pomalidomide, bortezomib, and carfilzomib have gained popularity over traditional chemotherapy because of higher response rates and survival. The increased response rate is at the expense of significant grade 3 and 4 toxicity, which can include myelosuppression, venous thromboembolism (VTE), and neuropathy depending on the regimen used.

  • Image not available. Thalidomide, lenalidomide, and pomalidomide are immunomodulatory agents that have antiangiogenic and anti-inflammatory activity. Thalidomide’s dose limiting toxicity is neuropathy. Lenalidomide is less neurotoxic, but can cause significant myelosuppression. Pomalidomide, the newest of this class, is currently only used in relapsed/refractory MM.

  • Image not available. The proteasome inhibitors, bortezomib and carfilzomib, are highly active in the treatment of MM, particularly those with high-risk cytogenetics.

  • Image not available. Autologous hematopoietic stem cell transplantation (HSCT) is used after induction in patients with reasonably good performance status to maximize complete remissions and prolong survival. Combining autologous HSCT with allogeneic HSCT is investigational and should be performed within a clinical trial.

  • Image not available. Maintenance therapies may be used in both transplant-eligible and ineligible patients. Current regimens typically include lenalidomide or bortezomib with the intent of increasing response rates and progression-free survival.

  • Image not available. Bisphosphonates are used to treat bone disease associated with MM, which results in decreased pain and skeletal-related events and improved quality of life.

  • Image not available. Salvage therapy for patients with relapsed or refractory MM can include any of the prior listed therapies and depends on patient’s performance status, risk category, and prior treatments used for induction.

Image not available. Multiple myeloma (MM) is a malignancy of plasma cells or immunoglobulin-producing B lymphocytes.1,2 The cancer is characterized by clonal proliferation and accumulation of a monoclonal immunoglobulin secreted from the plasma cell that can be measured in the plasma or urine. Patients with MM often have osteolytic bone lesions at the time of diagnosis, which is probably related to various bone-mobilizing cytokines secreted from the MM clone and bone marrow stromal cells. Other clinical manifestations include end-organ damage such as renal insufficiency, hypercalcemia, and anemia. The treatment of MM often consists of two or three drug combinations incorporating a proteasome inhibitor and immunomodulator. These regimens have improved response rates and outcomes compared to conventional chemotherapeutic agents. Although therapy is not currently curative, MM continues to be a remarkable example of bench-to-bedside translation in new drug development.

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