let's recode the building blocks
Multiple myeloma is a cancer of certain cells in the blood, called plasma cells. Normal plasma cells are found in the bone marrow and make up an important part of the immune system. The body of cells in the immune system work together to fight infections and disease. Multiple myeloma occurs when plasma cells become cancerous and start to spread throughout the bloodstream.i By nature, plasma cells are durable, with some having life spans of over 60 years,ii but some genetic modifications enable cancerous cells to evade detection by the immune system.iii
What are the symptoms?
Symptoms of multiple myeloma can include bone pain and weak bones, anemia, numbness and muscle weakness. The most common symptom is bone pain, usually of the lower back or ribs. In most cases, movement worsens the pain, which may be mild, moderate or severe. Affected individuals are usually more susceptible to fractures than the general population and may experience repeated fractures of affected bones. The bones of the spine may become involved, potentially collapsing and resulting in spinal cord compression. Compression of the spinal cord results in pain, weakness and numbness in the arms and legs.iv
Other common symptoms of multiple myeloma are fever and frequent infections. This happens because multiple myeloma affects cells in the immune system, so people with active multiple myeloma have a reduced ability to fight infections.v
How common is multiple myeloma?
Multiple myeloma is the second most common blood cancer in the world.vi,vii It accounts for over 10% of hematological malignancies, which are defined as cancers of the blood or bone marrow.viii,ix
In 2019, over 32,000 individuals in the U.S. were diagnosed with multiple myeloma.iv According to the American Cancer Society, an estimated 32,270 new cases were diagnosed in the U.S. in 2020 and about 12,830 deaths were expected to occur.i It is believed that approximately 100,000 Americans currently have the disease.iv
How is it diagnosed?
Multiple myeloma can be difficult to diagnose. To make an accurate diagnosis, physicians will rely on several factors, including physical evaluation, a list of symptoms, your medical history and the results from a range of diagnostic tests, including blood tests, urine tests and bone or bone marrow tests.x
What causes it?
The cause of multiple myeloma is not known, and currently there is no cure.xi
Risk factors for myeloma include increasing age, black race, male sex, and family history.xi Another risk factor is monoclonal gammopathy of undetermined significance (MGUS), a rare condition in which an abnormal protein called monoclonal protein is detected in the blood. In some cases, MGUS may progress over time to multiple myeloma or other forms of blood cancer.xiii
In recent years, with the introduction of several new treatment options, the outlook for multiple myeloma patients has improved markedly. However, without a cure or a treatment that addresses the underlying immunology of the disease, the disease worsens and patients experience periods of remission and relapse.
When does multiple myeloma become relapsed or refractory?
Despite advances in treatment, multiple myeloma is characterized by the persistence of residual disease and multiple periods of remission and/or relapse.xiv,xv,xvi Most patients experience relapse, or return of their cancer, following initial treatment and each relapse can worsen a patient’s prognosis for improvement and survival living with the disease, regardless of having subsequent treatment.xvii,xviii,xix
Relapsed multiple myeloma is disease that reoccurs after initial treatment and refractory multiple myeloma is disease that is progressing despite active treatment. Patients with relapsed or refractory multiple myeloma have fewer effective treatment options because they have become resistant to newer and commonly used drugs, thereby making late-stage multiple myeloma difficult to treat effectively.xx
What is the individual impact for patients?
In multiple myeloma, the spread of cancerous plasma cells causes osteolysis, or progressive bone destruction, resulting in severe bone pain, fractures, and hypercalcemia (excessively high calcium levels in the blood), as well as kidney damage and anemia.xxi,xxii
Multiple myeloma is an incurable disease and almost all patients eventually relapse.xvii
When patients relapse, their disease becomes less responsive, resulting in shorter response durations,xxiii,xvi the length of time a patient continues to respond to therapy without their disease growing or spreading. Relapse also results in decreased quality of lifexvi and continued immune system dysregulation.xxiv
In the U.S., roughly 29% of patients with newly diagnosed MM die within one year of diagnosis; the 5-year survival rate is approximately 52%.xxv,xxvi
Patients with relapsed or refractory multiple myeloma can receive several rounds of treatment and have fewer treatment options, leaving them in significant need of new therapies.xx,xxvii,xxviii
iAmerican Cancer Society. About Multiple Myeloma. Available at https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf Accessed January 2021. iiAndraud M, et al. PLoS Comput Biol. 2012;8(3):e1002418. iiiKumar SK, et al. Hematology Am Soc Hematol Educ Program. 2017;2017(1):518-524. ivNational Organization for Rare Disorders (NORD). Rare Disease Database: Multiple Myeloma. Available at https://rarediseases.org/rare-diseases/multiple-myeloma/. Published 2016. Accessed January 2021. vMumoli N, Cei M. Multiple myeloma and fever of unknown origin: a need for therapy. Br J Cancer. 2005 Jul 25; 93(2):266. viSiegel RL, Miller KD, Jemal A. Cancer Statistics. CA Cancer J Clin. 2019;69:7-34. viiBray F, Ferlay J, Soerjomataram I. et al. CA Cancer J Clin. 2018;0:1-31. viiiKyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860-1873. ixRajkumar SV, Kyle RA, Goldman L, Ausiello D. Plasma cell disorders. Cecil Textbook of Medicine, 23rd ed. pg. 1426-1437. Philadelphia, PA: Saunders; 2007. xMultiple Myeloma Research Foundation (MMRF). Diagnosis. Available at https://themmrf.org/multiple-myeloma/diagnosis/. Accessed January 2021. xiDeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 1997. xiiAlexander DD, et al. Int J Cancer. 2007;120(suppl 12): 40-61. xiiiGenetic and Rare Diseases Information Center (GARD). Monoclonal gammopathy of undetermined significance Available at https://rarediseases.info.nih.gov/diseases/7034/monoclonal-gammopathy-of-undetermined-significance. Accessed January 2021. xivDurie BGM, et al. International Myeloma Foundation. North Hollywood, CA; 2017. xvJagannath, et al. Expert Rev Hematol. 2016;9:707-717. xviKumar SK, et al. Mayo Clin Proc. 2004;79:867-874. xviiNijhof IS et al. Drugs. 2018;78:19–37. xviiiUsmani SZ, et al. Blood. 2016;128(1):37-44. xixLonial S, et al. Lancet. 2016;387(10027):1551-60. xxKumar SK, et al. Leukemia. 2017; 31(11):2443-2448. xxiPluta RM. JAMA. 2010;304:2430. xxiiGiuliani N, et al. Blood. 2006;108:3992-3996. xxiiiBird SA, Boyd K. Palliat Care Soc Pract. 2019;13:1-13. xxivBoland E, et al. J Pain Symptom Manage. 2013;46(5):671-680. xxvNCI SEER. https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed January 2021. xxviCosta LJ, et al. Leukemia. 2015;29:1616-1618. xxviiUsmani SZ, et al. Blood. 2016;128(1):37-44. xxviiiLonial S, et al. Lancet. 2016;387(10027):1551-60.