eMedicine Specialties > Orthopedic Surgery > Neoplasms

Myeloma: Treatment & Medication

Author: Seema S Rizvi, MD, Associate Medical Director, Lutheran Care Center
Coauthor(s): Howard A Chansky, MD, Associate Professor, Department of Orthopedics and Sports Medicine, University of Washington Medical Center
Contributor Information and Disclosures

Updated: May 29, 2009

Treatment

Medical Care

Although multiple myeloma (MM) remains incurable, several drug therapies are valuable in the treatment of patients with MM. A combination of melphalan and prednisone remains the standard chemotherapy. As monotherapy or in combination, interferon alfa-2b and prednisone modestly prolong the disease-free interval. Early evidence suggests that bisphosphonates may be effective in treating bone pain and in decreasing the likelihood of lesion recurrence.^{6,7,8,9,10,11,12}

The resistance mechanisms to chemotherapy in MM are reduced drug concentration at the target site of action, alterations in the drug target, and inhibition of drug-induced apoptosis. Factors mediating myeloma cell growth, patient survival rates, and the complex interaction of myeloma cells with the bone marrow microenvironment have provided a framework for the rational design of therapeutic agents that may ultimately lead to improved disease-free survival and, potentially, a cure. Overall, the care of patients with MM is complex and should focus on treatment of the disease process and any associated complications.^13,14,15

Chemotherapy

Patients with symptomatic MM require chemotherapy. In asymptomatic patients with MM, treatment is delayed until disease clinically progresses or until serum or urine levels of M protein substantially increase.

Chemotherapy with melphalan-prednisone (MP) is the standard treatment for MM. It consists of melphalan 9 mg/m² and prednisone 100 mg given on days 1-4, with courses repeated at 4- to 6-week intervals for at least 1 year.

The M-component level in serum and/or urine is an indicator of the tumor burden; its reduction after chemotherapy is used as a sign of response. A 50% reduction in M-component is considered a good clinical response (according to the Chronic Leukemia-Myeloma Task Force). MP induces a response in 50-60% of patients with MM. Disappearance of the M component on electrophoresis occurs in only 3% of patients, and cure is extraordinarily rare.

Combination chemotherapies may be appropriate. Vincristine, Adriamycin, and dexamethasone (VAD) chemotherapy is used in MM treatment. It is the best standard-dose treatment for patients in whom relapse occurs. The following treatments may be helpful: high-dose chemotherapy (melphalan) with stem cell transplantation, low-dose therapy with melphalan (essentially palliative), and immunotherapy with bortezomib.

For MM therapy, the MP regimen no longer is the criterion standard, as it is suitable for less than 50% of patients. Alternative approaches, such as VAD-based regimens and high-dose chemotherapies with stem-cell support are preferred for most patients.

High-dose chemotherapy in cases of autotransplantation has shown encouraging complete remission rates over several years in phase 1 studies, and it was superior to conventional therapy in a randomized study. Autologous peripheral blood stem cells (PBSCs) in support of high-dose melphalan is now considered standard therapy for young patients with myeloma. New active drugs include immunomodulatory agents, such as thalidomide and CC-5013 (Revimid; Celgene, Warren, NJ) and the proteosome inhibitor PS 341 (Velcade; Millenium, Cambridge, Mass).

Radiation therapy

Myeloma is sensitive to radiation therapy. If the pain is mild and if less than 50% of the bone is involved, a course of irradiation can be initiated. Radiation treatment can result in additional early bone loss due to inflammation, and weight bearing should be limited for the first 4-6 weeks.

American Society of Clinical Oncology (ASCO) patient guide

For bone resorption, bisphosphonates are specific inhibitors of osteoclastic activity. They are used to treat bone resorption. Intravenous pamidronate is effective in preventing skeletal complications.

Lytic disease or fracture may be observed on plain radiographs.

Pamidronate at 90 mg delivered intravenously over at least 2 hours or zoledronic acid at 4 mg given over 15 minutes every 3-4 weeks are recommended. For all patients receiving chronic pamidronate or zoledronic acid therapy, the ASCO panel recommends urinalysis every 3-6 months to test for albuminuria and azotemia. In patients with preexisting renal disease and a serum creatinine value of less than 265 µmol/L or less than 3 mg/dL, no change in dose, infusion time, or interval is required.

Thalidomide therapy

In a Mayo Clinic study, nearly one third of patients with advanced MMs in whom current standard chemotherapy or stem cell transplantation failed were shown to respond to thalidomide for a median duration of nearly 1 year.¹⁶ Thalidomide is useful in the treatment of patients with relapsing and refractory MM. Its antiangiogenic properties have become increasingly apparent as a critical step in the proliferation and spread of malignant neoplasm.^17,18

Allotransplants

Allotransplants have markedly reduced activity; therefore, the use of nonmyeloablative regimens (mini-allotransplantation) may hold promise for more widely exploiting this feature.^19,20

Surgical Care

Surgical care consists of prophylactic fixation of pending fractures, decompression of the spinal cord when indicated, and treatment of pathologic fractures.

Prophylactic treatment of impending fractures and the treatment of pathologic fractures may involve bracing. In general, bracing is not effective for the long bones, though it may be effective for treating spinal involvement without neurologic compromise.

Intramedullary fixation is the procedure of choice when surgery is necessary. If the metaphysis or joint surface is involved, resection of the diseased bone and reconstruction with a total joint or, more typically, a hemiarthroplasty is indicated. Modular implants may be required. Severe destruction of the diaphysis may require reconstruction with combinations of methylmethacrylate, intramedullary nails, or resection and prosthetic replacement.

Consultations

Patients with multiple myeloma have significant systemic comorbidities. These include potentially severe hematologic, infectious, and metabolic diseases. The orthopedic surgeon treating the skeletal disease in a patient with myeloma should work in conjunction with the radiation oncologists and the medical oncologists.

Activity

In general, patients with activity-related pain in either the femur or the tibia should be given a walker or crutches until a radiographic workup has been completed. Radiation therapy elicits an inflammatory response, and for the first 6 weeks or so, bony resorption may actually weaken the target bone. Prophylactic treatment of an impending fracture is usually easier than reconstruction of a pathologic fracture. Therefore, one should have a low threshold for initiating protected weight bearing.

Medication

The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Immunomodulatory agents

These regulate key factors of the immune system.

Thalidomide (Thalomid)

Immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.

Interferon alfa-2b (Intron A)

Recombinant DNA product. Mechanism of antitumor activity not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may be important.

Antineoplastic agents

These inhibit cell growth and proliferation.

Vincristine (Oncovin, Vincasar PFS)

Inhibits microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at metaphase stage.

Doxorubicin (Adriamycin, Rubex)

Cytotoxic anthracycline antibiotic. Inhibits topoisomerase II and produces free radicals, which may cause DNA destruction. Combination of these 2 events can in turn inhibit growth of neoplastic cells. Used in combination with other chemotherapy drugs.

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Melphalan (Alkeran)

Inhibits mitosis by cross-linking DNA strands.

Bortezomib (Velcade)

First proteasome inhibitors (anticancer agents) approved. Proteasome pathway is enzyme complex in all cells; degrades ubiquitinated proteins that control cell cycle and cellular processes and maintains cellular homeostasis. Reversible proteasome inhibition disrupts pathways supporting cell growth, decreasing cancer cell survival.

• Search for CME/CE on This Topic »

• Multiple Myeloma (Hematology)
• Multiple Myeloma (Radiology)
• Amyloidosis, Primary Systemic (Dermatology)
• Hyperviscosity Syndrome (Emergency Medicine)

• Myeloma Treatment
• Blood and Lymphatic System Center
• Myeloma Overview
• Myeloma Causes
• Myeloma Symptoms

• Bisphosphonates are Essential Component of Multiple Myeloma Treatment, Says Expert Panel
• Low-Dose Dexamethasone Plus Lenalinomide Established as Initial Therapy for Myeloma
• Vitamin D Deficiency Adversely Impacts Multiple Myeloma

• Pathogenesis and Management of Myeloma Bone Disease
• Serum Free Light Chain Measurement Aids the Diagnosis of Myeloma in Patients With Severe Renal Failure
• Reversibility of Renal Impairment in Patients With Multiple Myeloma Treated With Bortezomib-based Regimens: Identification of Predictive Factors

• Multiple Myeloma Resource Center