What Is New in Multiple Myeloma?

Multiple myeloma (MM) is a treatable but incurable hematologic cancer that affects plasma cells in the bone marrow. This rare cancer accounts for 1% to 2% of new cancer cases each year,^1-3 or a little more than 30,000. Although there is no cure for MM, there have been tremendous advances in therapy over the past 10 years, which has led to significant improvements in the overall survival rate, with the 5-year survival at close to 50%.²

Disease Overview

In MM, plasma cells proliferate in an uncontrolled fashion in the bone marrow space. Cancerous plasma cells produce an antibody, a monoclonal protein, that can accumulate in the blood or urine, leading to kidney function abnormalities and other organ dysfunction.^2-5 Other diagnostic criteria of MM include anemia, biomarkers representative of active disease, hypercalcemia, and skeletal destruction. However, 20% of patients present with no symptoms.^3,4

The cause of MM is not known, but most patients have genetic alterations in their plasma cells that lead to disease development. Diagnosis is more common in males, is 2 to 3 times more common in African Americans and is less common in those of Japanese and Latino ancestry.^2,3 MM also is a disease of aging adults, with the average age of diagnosis being 69 years. The incidence of MM is expected to increase significantly over the next 50 years, because of the expanding older population in the United States.

Treatment Overview

The goals of treatment are to control disease activity, improve symptoms (anemia, bone pain/fractures, and high calcium levels), reduce frequent infections, and prolong remission, with the mainstay of treatment revolving around chemotherapy and stem cell transplant. Initial chemotherapy, with a combination of drugs, has response rates approaching 100%, and half or more of patients achieve a complete response. Other treatment options are autologous stem cell transplant, radiation, and surgery, which can help lessen the occurrence and severity of adverse effects (AEs).

Drugs used to treat MM include corticosteroids such as dexamethasone and prednisone, alkylating agents, and, sometimes, anthracyclines.^3,4 Newer agents, such as immunomodulators, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies, provide great treatment options with advances in outcomes.⁴

Initial treatment is usually combination chemotherapy with 3 drugs favored over 2, unless patient-limiting factors prevent multiple agents. Patients are also often offered transplant because of strong data showing longer disease-free and better overall survival. They are usually treated continuously, because of evidence showing that it is better than a defined treatment duration. If a patient relapses, they can get transplanted again, can try a new drug, or enroll in a clinical trial.

Future Trends

Many new therapies are being developed for MM. The promising programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1), or checkpoint, inhibitors interfere with the mechanism by which cancer cells hijack and prevent T cells from attacking them in the body. These drugs allow immune cells to attack tumor cells. They are not the standard of care right now and are not as effective by themselves, but they do show promise in combination with other therapies.^6,7

Chimeric antigen receptor (CAR) T-cell therapy is when T cells are removed from a patient and engineered in the lab to recognize a protein on the surface of cancer cells. B-cell maturation antigen (BCMA) is the most common protein, but 4 types of CAR T cells have been described, and several show a lot of promise.^7,8 However, the cost of therapy will be a big discussion point in the years ahead, with a 1-time dose of CAR T cell therapy estimated at $475,000.

A highly modified antibody, Bi-specific T-cell engager, nicknamed a BiTE molecule, has been used to target tumor cells and recruit T cells in the patient that would otherwise not recognize it. This is an in vivo way of doing what CAR T cells do, and it is just beginning to be tested. Additional new therapies being developed are other histone deacetylase inhibitors and a nuclear protein transport inhibitor.⁷

In 2018, the FDA approved a new bone agent, denosumab (Xgeva) for skeletal-related events pertaining to MM. Denosomab affects bone resorption by inhibiting the RANK ligand. It has similar efficacy to zolendronic acid, with better activity in patients with kidney dysfunction, not as many flu-like symptoms, and more convenient administration. However, it still carries the AE of osteonecrosis of the jaw.

In the years ahead, initiatives may lead to groundbreaking developments in the treatment of MM. This precision medicine project involves gathering a large amount of data that includes DNA sequencing (eg, myeloma bone sample) with the intent of being able to tailor treatments to each patient.^7,8 Genetic sequencing, with providers able to quickly identify mutations in clinic, is also a goal of future care, to guide prevention therapy and treatment selection.⁷

Conclusion

Many exciting developments are on the horizon for MM. Checkpoint inhibitors, CAR T-cell therapy, precision medicine, and other new therapies show promise for treatment in the years ahead.

Joanna Lewis, PharmD, MBA, is a clinical pharmacist who is passionate about medication safety, clinical quality, leadership development, and regulatory affairs. She received her pharmacy degree from the Medical University of South Carolina and is an active member of the ASHP. She has worked in a variety of practice settings, most recently as a coordinator at Duke University Hospital in Durham, North Carolina.

References

• American Cancer Society. Key statistics about multiple myeloma. ACS website. cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Updated February 28, 2018. Accessed July 14, 2018.
• National Cancer Institute. Cancer stat facts: myeloma. seer.cancer.gov/statfacts/html/mulmy.html. Accessed July 14, 2018.
• Smith D, Yong K. Multiple myeloma. BMJ. 2013; 346:f3863. doi: 10.1136/bmj.f3863.
• Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111(6):2962-2972. doi: 10.1182/blood-2007-10-078022.
• Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011;364(11):1046-1060. doi: 10.1056/NEJMra1011442.
• Rajkumar SV, Kyle RA. Progress in myeloma — a monoclonal breakthrough. N Engl J Med. 2016;375(14):1390-1392.
• Durie B. Top five trends in myeloma news for 2018. International Myeloma Foundation. myeloma.org/blog/dr-duries/top-five-trends-myeloma-news-2018. Published January 11, 2018. Accessed July 22, 2018.
• Mikkilineni L, Kochenderfer J. Chimeric antigen receptor T-cell therapies. Blood. 2017;130(24):2594-2602. doi: 10.1182/blood-2017-06-793869.