On the Horizon for Multiple Myeloma: Update on Novel Agents, Bone Therapies

Michael Marlan Mohundro, PharmD, and Brice Labruzzo Mohundro, PharmD
Published: Wednesday, Sep 12, 2012
malignant plasma cells illustration

Illustration depicts the malignant plasma cells that develop in multiple myeloma. The American Cancer Society estimates about 21,700 new cases will be diagnosed in 2012.

Treatment of multiple myeloma (MM) remains highly individualized, with multiple factors that play a role in determining the best course of therapy. Patient-specific criteria such as age of onset, whether the patient is symptomatic at the time of diagnosis, and any detected high-risk cytogenic abnormalities are all considerations when selecting a regimen. Newer agents such as bortezomib and lenalidomide in combination with lowdose steroids have replaced more toxic chemotherapeutic regimens for primary induction and have led to significant increases in progression-free survival. Depending on duration of response prior to relapse, patients may be rechallenged with the same regimen, switched to an alternative, or may undergo hematopoietic cell transplant (HCT), which remains a highly effective treatment option for patients who are candidates. However, the cost of transplantation remains high, and some patients may require a second transplantation if the initial response is incomplete. With the availability of newer agents for salvage therapies in refractory or relapsed patients, the reliance on HCT may decrease, potentially lowering healthcare costs. In addition, the availability of orally active agents may decrease the need for outpatient infusions, thus decreasing the overall costs associated with treatment and improving patient satisfaction. Finally, combination regimens that use lower doses may prove to be less toxic, as well as more effective. Even though MM only accounts for approximately 1% of all cancers in the United States, with 75 million “baby boomers” now reaching the median age of diagnosis, the increased number of cases could have a substantial impact on healthcare costs.

Although MM is a fairly uncommon cancer, it is the most commonly occurring blood cancer.1 The American Cancer Society estimates that in 2012, approximately 21,700 new cases will be diagnosed and approximately 10,710 deaths will occur as a result of MM.2 Patients with MM may present with bone pain (especially in the back), fatigue often caused by anemia, pathologic fracture, weight loss, and/or paresthesias. Some patients have no symptoms at the time of diagnosis.3 MM occurs when vast amounts of abnormal plasma cells are found in bone marrow. Additionally, there is an overproduction of IgG, IgA, IgD, IgE, or monoclonal light chains known as Bence-Jones proteins.4 Treatment of MM is complex. Patients with stage II or III MM who are considered to have good performance status are candidates for stem cell transplantation. Induction therapy with dexamethasone monotherapy or a combination of dexamethasone and thalidomide before stem cell harvesting is an option for patients; however, high-dose chemotherapy with vincristine, melphalan, cyclophosphamide, and prednisone alternating with vincristine, carmustine, doxorubicin, and prednisone along with bone marrow transplant has been associated with increased survival in patients. Patients who are not stem cell candidates may be treated with thalidomide, melphalan, and prednisone. Patients who are not responding or who relapse with this regimen may be treated with vincristine, doxorubicin, and dexamethasone. 5 Refractory or relapsing MM is common. Currently, regimens available for these patients contain thalidomide, lenalidomide, or bortezomib. On the horizon to treat patients with relapsed or refractory myeloma are a new generation of proteasome inhibitors, immunomodulatory agents, and deacetylase inhibitors, which are currently being investigated in clinical trials.

Immunomodulating Agents


Despite MM being an incurable disease, immunomodulatory drugs (IMiDs) have demonstrated effectiveness in the treatment of MM. IMiDs have been investigated for both first-line and maintenance therapies.6 Thalidomide was the first drug in this class and subsequently lenalidomide was approved by the FDA.6 Pomalidomide is the newest IMiD under investigation and several phase I and II trials have been completed. While the drug is a chemical analogue of thalidomide, it appears to have a much greater potency in stimulating the proliferation of T-cells as well as increasing natural killer cell activity.6 Additionally, the drug works through inhibition of blood cell growth and modulates the levels of inflammatory and regulatory cytokines. IMiDs have also been shown to directly induce apoptosis in plasma cells.6 Phase I, II, and III clinical trials are currently under way to evaluate the drug in combination with dexamethasone, as well as in combination with bortezomib, doxorubicin, and cyclophosphamide.7

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize OutcomesOct 31, 20182.0
Hematology Briefings™: Advancing Care and Improving Outcomes for Patients With Pyruvate Kinase DeficiencyOct 31, 20181.0
Publication Bottom Border
Border Publication