Multiple Myeloma: Advances in Treatment Bring Hope

Yvette C. Terrie, BSPharm, RPh
Published Online: Friday, May 17, 2013

New therapies advance the treatment of this hematologic cancer.
Multiple myeloma ranks as the second-most prevalent hematologic cancer after non-Hodgkin’s lymphoma and accounts for an estimated 10% of all cancers that affect the blood.1-3 According to the National Cancer Society, an estimated 22,350 adults will be newly diagnosed with multiple myeloma in 2013 and an estimated 10,710 deaths are expected.1,2

Pathology of Multiple Myeloma

Multiple myeloma is a malignant neoplasm of plasma cells that accumulates in the bone marrow, resulting in bone destruction and marrow failure; skeletal destruction, hypercalcemia, anemia, and renal failure also occur.1-5 As multiple myeloma progresses, the malignant cells accumulate in the bone marrow and in turn cause painful bone lesions that prevent normal blood cell production.4,6,7 Although currently there is no cure, continual advances in therapy have greatly improved survival rates.

To date, the exact etiology of multiple myeloma is unknown, but the disease occurs primarily in individuals in their 60s and is more prevalent in men and in African Americans.1-3,7 An estimated 5% to 10% of those with multiple myeloma are younger than 40 years.3,4

Research has implicated possible factors in multiple myeloma’ s etiology , including genetic, occupational, or environmental causes; monoclonal gammopathy of undetermined significance; radiation exposure; infections; and chronic inflammation. Some studies have found an increased risk among those individuals with significant exposures to chemicals in agricultural and petrochemical occupations.7,8 Results from the EPILYMPH study concluded that there appears to be an association between multiple myeloma and farm work, printing, and cleaning.9 Exposure to herbicides, insecticides, plastics, heavy metals, and petroleum products may be possible risk factors, according to some studies, along with family history of multiple myeloma.2,7,8,10, The majority of multiple myeloma cases appear in those with no risk factors, however.7,8

Symptoms of Multiple Myeloma

Typically the majority of patients with multiple myeloma are asymptomatic in the early stages and an estimated 20% present with mild symptoms or no symptoms at the time of diagnosis.10 Multiple myeloma is often discovered through routine blood screening when patients are being evaluated for unrelated health problems.8 Bone pain is considered to be the most prevalent presenting symptom.7-10 Table 1 lists other symptoms associated with the disease.

Managing Multiple Myeloma
The development of the proteasome inhibitor bortezomib in the past decade represented ann advance in multiple myeloma therapy.10-12 The immunomodulatory drugs lenalidomide and thalidomide have resulted in significant improvement outcomes for multiple myeloma patients as well, and are considered to be highly effective.10-13 Currently, there is no cure for multiple myeloma; in addition to these 3 agents, treatment options include chemotherapy, immunosupression, radiation, stem cell transplant, and surgical care.8-15

Treatment for multiple myeloma is always tailored to the specific stage of the disease and the patient’s age, renal function, overall health status, and other needs. Often treatment involves a combination of pharmacologic agents. Chemotherapy is often employed to reduce disease burden and bisphosphonates are often used to enhance bone healing and provide secondary prophylaxis against skeletal-related issues.7,8,16-18 Erythropoietin is often prescribed to treat anemia, either alone or in conjunction with chemotherapy.17-19 Corticosteroids are also an important component of multiple myeloma therapy.7,16-18 Dexamethasone and prednisone are the most commonly prescribed and can also be helpful to decrease the nausea and vomiting associated with chemotherapy.8,10,15-18

New Therapies
Results from various clinical trials demonstrate that many newer agents for multiple myeloma have doubled the survival rate of many patients.8-15 In February 2013, the FDA approved the oral therapy pomalidomide (Pomalyst) for use in the treatment of relapsed or refractory multiple myeloma.19,20 It is indicated specifically for those patients who have received at least 2 prior therapies, including lenalidomide and bortezomib, whose disease did not respond to treatment and progressed within 60 days of the last treatment.19,20 This agent is the third treatment option from the class of immunomodulatory agents that include lenalidomide and thalidomide.20,21 Pomalidomide is considered a more potent analogue of thalidomide.19 The recommended dose for pomalidomide is 4 mg, compared with 800 mg for thalidomide and 25 mg for lenalidomide.19 Like other drugs in this class, it carries a boxed warning regarding potential to cause birth defects.19-20

In July 2012, the FDA approved Kyprolis (carfilzomib) for injection, a proteasome inhibitor indicated for the treatment of patients with multiple myeloma who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and who have demonstrated disease progression on or within 60 days of completion of the last therapy.21,22

Table 2 provides a closer look at therapies for multiple myeloma. For more information about multiple myeloma treatment, the National Comprehensive Cancer Network recently released updated guidelines for the treatment of multiple myeloma, which can be found at www.nccn.org.




New Research

According to the American Cancer Society, various drugs are being investigated for multiple myeloma, including those that may aid in blocking blood vessel growth in multiple myeloma patients. Another class of drug is being tested to block a molecule in tumor growth known as farnesyl transferase; other agents are being investigated for their potential to block growth factors and reduce bone destruction in patients with multiple myeloma.28

Conclusion

Multiple Myeloma Resources
International Myeloma Foundation
www.myeloma.org
National Cancer Institute
www.cancer.gov
Multiple Myeloma Research Foundation
www.themmrf.org
American Cancer Society
www.cancer.org
The Myeloma Beacon
www.myelomabeacon.com
Although there is no cure for multiple myeloma, patients are benefiting from the significantly improved treatment options that have emerged in the past decade and improve survival rate and decrease pain and complications.27 A diagnosis of multiple myeloma presents challenges for its patients, but ongoing research to help improve the overall quality of life of multiple myeloma patients offers a glimmer of hope.

Pharmacists can be a source of information and empower patients to make informed decisions about their health. Knowledge about the disease, its management, and possible treatments is a patient’s best defense in the fight against multiple myeloma.


Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia.

References
  1. What is multiple myeloma? The Multiple Myeloma Research Foundation website. www.themmrf.org/living-with-multiple-myeloma/newly-diagnosed-patients/what-is-multiple-myeloma/. Accessed March 9, 2013.
  2. What you need to know about multiple myeloma. NIH National Cancer Institute website. www.cancer.gov/cancertopics/wyntk/myeloma.pdf. Accessed March 9, 2013.
  3. Multiple myeloma. International Myeloma Foundation website. http://myeloma.org/pdfs/PH2010-Eng_l2.pdf. Accessed March 9, 2013.
  4. Anderson KC, Alsina M, Bensinger W, et al. Multiple myeloma, version 1.2013. J Natl Compr Canc Netw. 201;11(1).
  5. Jagannath S. Pathophysiolgical underpinnings of multiple myeloma progression. J Manag Care Pharm. 2008;14(7 suppl):7-11.
  6. Hawley TS, Riz I, Yang W, et al. Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1 [published online January 22, 2013]. Am J Hematol.
  7. What is multiple myeloma? American Cancer Society website. www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed March 5, 2013.
  8. Seiter K. Multiple myeloma. Medscape website. http://emedicine.medscape.com/article/204369-overview. Accessed March 9, 2013.
  9. Perrotta C et al. Multiple Myleoma and lifetime occupation: results from EPILYMPH study. J Occup Med Toxicol. 2012;7(1):25.
  10. Advances in the Treatment of Multiple Myeloma. Cancer Care website. www.cancercare.org/publications/12-advances_in_the_treatment_of_multiple_myeloma. Accessed March 9, 2013.
  11. Palumbo A, Rajkumar SV. Treatment of newly diagnosed myeloma. Leukemia. 2009; 23(3):449-456.
  12. Watanabe R. et al Current approaches for the treatment of multiple myeloma [published online March 10, 2013]. Int J Hematol.
  13. Chustecka Z. New insight into drug action in multiple myeloma. Medscape website. www.medscape.com/viewarticle/755249. Accessed March 5, 2013.
  14. Bensinger WI. Role of autologous and allogeneic stem cell transplantation in myeloma. Leukemia. 2009;23(3):442-448.
  15. Ocio EM, Mateos MV, Maiso P, Pandiella A, San-Miguel JF. New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings. Lancet Oncol. 2008; 9(12):1157-1165.
  16. Treatment options for multiple myeloma by stage. American Cancer Society website. www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-treating-by-stage. Accessed March 7, 2013.
  17. Multiple myeloma treatment overview. Multiple Myeloma Research Foundation website. www.themmrf.org/assets/mmrf-treatment-overview.pdf. Accessed March 7, 2013.
  18. Drugs approved for multiple myeloma and other plasmaneoplasms. NIH National Cancer Institute website. www.cancer.gov/cancertopics/druginfo/multiplemyeloma. Accessed March 7, 2013.
  19. Pomalyst prescribing information. Celegene website. www.pomalyst.com/docs/prescribing_information.pdf. Accessed March 7, 2013.
  20. Novel myeloma drug wins FDA approval. MedPage Today website. www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/37282. Accessed March 9, 2013.
  21. Kryprolis prescribing information. Onyx Pharmaceuticals website. www.onyx.com/therapies/kyprolis-carfilzomib-for-injection. Accessed March 7, 2013.
  22. Carfilzomib receives FDA nod for multiple myeloma. Medscape website. www.medscape.com/viewarticle/767819. Accessed March 7, 2013.
  23. Bortezomib prescribing information. Millennium Pharmaceuticals website. www.velcade.com/files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf. Accessed March 7, 2013.
  24. Thalomid prescribing information. Celgene Pharmaceuticals website. www.thalomid.com/. Accessed March 7, 2013.
  25. Revlimid prescribing information. Celegene website. www.revlimid.com/.   Accessed March 7, 2013.
  26. FDA approved pomalidomide for multiple myeloma. Medscape website. www.medscape.com/viewarticle/779048. Accessed March 7, 2013.
  27. Multiple Myeloma. Merck Manual for Healthcare Professionals Online Edition. www.merckmanuals.com/professional/hematology_and_oncology/plasma_cell_disorders/multiple_myeloma.html?qt=multiple myeloma&alt=sh. Accessed March 5, 2013.
  28. What’s new in multiple myeloma research and treatment? American Cancer Society website. www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-new-research. Accessed March 8, 2013.


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