- Multiple myeloma (MM) is a cancer that develops in plasma cells, leading to excessive production of a monoclonal immunoglobulin.
- 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 an M-protein spike on plasma or urine electrophoresis confirms the diagnosis.
- Most patients require treatment after diagnosis, but treatment can be deferred in patients with smoldering (asymptomatic) MM. In patients with symptomatic disease, treatment produces benefits in various measures of survival and quality of life.
- Thalidomide, lenalidomide, or bortezomib plus dexamethasone are commonly used induction regimens. They produce higher complete remission rates compared with the classic regimens of melphalan plus prednisone and VAD (vincristine, doxorubicin, and dexamethasone). The increased response rate is at the expense of significant grade III and IV toxicity, which can include myelosuppression, venous thromboembolism (VTE), and neuropathy depending on the regimen used. These novel agents can be added to chemotherapy (melphalan, liposomal doxorubicin, cyclophosphamide, or VAD-like chemotherapy) as part of induction and results in substantially higher response rates. Novel agents can also be combined to produce more active regimens.
- Bortezomib-based regimens are commonly used to treat newly diagnosed patients with high-risk disease and patients with relapsed MM.
- Lenalidomide is more potent and better tolerated than thalidomide and is the most commonly used immunomodulatory drug.
- A host of new drugs are being studied and integrated into treatment of relapsed MM, including carfilzomib, pomalidomide, vorinostat, and bendamustine. Carfilzomib is a very active agent and is currently being studied as induction therapy in newly diagnosed patients.
- Melphalan plus prednisone is not used in transplant candidates as part of induction but commonly used in transplant-ineligible patients combined with thalidomide, lenalidomide, or bortezomib.
- 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 must be considered investigational and should be performed under clinical trial.
- Maintenance therapies can be used in both transplant-eligible and -ineligible patients. Current regimens usually include lenalidomide or bortezomib with the intent of increasing response rates and progression-free survival.
- Bisphosphonates are used to treat bone disease associated with MM, which results in decreased pain and skeletal-related events and improvement in quality of life.
- Salvage therapy for patients with relapsed or refractory MM can include any of the prior listed therapies, depending on performance status of the patient, risk category of the patient, and prior treatments used for induction.
On completion of the chapter, the reader will be able to:
Describe the malignant cell of multiple myeloma (MM) and the methods used to diagnose the disease.
Explain the relationship between MM pathophysiology and disease-related complications.
Differentiate between monoclonal gammopathy of undetermined significance (MGUS), smoldering MM, and active MM as it relates to disease-related complications and initial treatment.
Describe those newly diagnosed patients who ...