Multiple Myeloma Overview

Hello. I’m Amy Pierre, and welcome to the Multiple Myeloma Center for Nurses. This video contains a brief overview of multiple myeloma.

Multiple Myeloma is a plasma cell malignancy. As you know, plasma cells are derived from B-lymphocytes, which are a key component in adaptive immunity, producing antigen-specific antibodies to fight pathogens.^5,6 The overgrowth of myeloma cells in the bone marrow crowds out normal plasma cells and prevents normal hematopoiesis.⁷ This often leads to anemia, thrombocytopenia and leukopenia, and associated symptoms. Patients can have precursor conditions that may progress to myeloma.^5,7 These patients are initially asymptomatic and remain undiagnosed. As the disease progresses, it can become symptomatic.⁷

Normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called M-protein found in blood and urine.⁸ Myeloma cells also secrete excess kappa and lambda free light chain proteins, abbreviated as FLCs, that are excreted in the urine.⁹ The ratio of kappa to lambda, referred to as the free light chain ratio, can predict disease progression from the intermediate precancerous condition to myeloma.⁹

Precursors to multiple myeloma are monoclonal gammopathy of undetermined significance, or MGUS, and smoldering myeloma.¹⁰ The annual risk of progression of MGUS to a malignancy ranges from 0.5% to 1.0%.^9,10 The risk of a patient’s progression from MGUS to active myeloma is only 1% per year.¹¹ The risk of progression from standard risk smoldering myeloma to active myeloma is 10% per year for the first 5 years following diagnosis, 3% per year for the next 5 years, and 1.5% per year thereafter.

Like myeloma, MGUS is defined by the presence of plasma cells in the bone marrow and M-protein in the serum.⁸ However, the number of plasma cells in the bone marrow is lower, less than 10%; the level of M-protein in serum is less than 3 grams per deciliter; and there is no organ damage or laboratory abnormalities with MGUS.^8,11

Patients with smoldering myeloma have higher levels of M-protein than those with MGUS. They also have a greater risk of progressing to symptomatic, or active, multiple myeloma.^8,11 Patients with smoldering myeloma have: At least 10% to 60% plasma cells in the bone marrow and/or a high M-protein level, defined as >3.0 g/dL; normal blood counts, calcium levels, and kidney function; and there’s no bone or organ damage.^8,11

Common presenting features in multiple myeloma include bone pain and fatigue.^4,8 Common laboratory features in myeloma include: anemia, elevated creatinine, and hypercalcemia.^8,12

The new definition of active multiple myeloma is: greater than 10% plasma cells in the bone marrow,¹³ or extramedullary plasmacytomas, and end-organ damage associated with plasma cell proliferation and classified by any one or more of the following CRAB features and myeloma-defining events.¹³

The 4 CRAB features include¹³ hypercalcemia—known as serum calcium levels >0.25 mmol/L (or >1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL) due to bone destruction, and changes in the bone marrow environment from the presence of excess plasma cells,¹³ renal insufficiency— defined as creatinine clearance <40 mL/min or serum creatinine >177 μmol/L (>2 mg/dL) caused by M-protein production, hypercalcemia, hyperuricemia, and dehydration, and can lead to edema, acidosis, and electrolyte imbalances,^7,13,14 anemia—which is hemoglobin >2 g/dL below the lowest limit of normal, or <10 g/dL due to kidney inability to produce erythropoietin and accumulation of myeloma cells in marrow, reducing space for erythropoiesis,^13,15 bone osteolytic lesions— one or more seen on skeletal radiograph, CT, or PET-CT imaging due to myeloma cell infiltration at skeletal sites, including spine, pelvis, skull, and long bones.^8,13,16

Myeloma-defining events may also include one or more of the following biomarkers of malignancy:¹³ ≥60% clonal plasma cells on bone marrow examination, a ratio of involved to uninvolved serum FLCs ≥100 with involved FLC ≥100 mg/L, and >1 focal lesion on MRI that is ≥5 mm in size.¹³ More information on end-organ damage is available in the CRAB video.

The Mayo Stratification of Myeloma and Risk-Adapted Therapy (abbreviated as mSMART) has been developed to classify myeloma risk based on cytogenetic abnormalities.¹² Each myeloma case is categorized as standard-, intermediate-, or high-risk.¹³ Patients who are high-risk tend to have shorter duration of response and overall survival.^13,17

Multiple myeloma is still incurable, but there has been an increase in median survival over the past decade, from 3-5 years to 8-10 years, thanks to expansion of treatment options and approved doublet, triplet, and quadruplet drug regimens.^18,19

There are several proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and several other classes of drugs and modalities of treatment, including cell and gene therapy, approved or in development.^8,18,19 As a result, multiple myeloma is now treated as a chronic cancer and the myeloma journey is made up of several periods of response and remission.⁸

One of the biggest challenges is managing disease-related and treatment-related complications throughout the course of disease so that patients can get the most out of each line of treatment.^8,9,19 The most common myeloma-associated complications are: bone destruction, renal disease, anemia, and neuropathy.⁸ Additional complications include thrombosis, fatigue, nausea, and immunoparesis.^20,21

Accumulation of M-protein can cause excess thickening of blood.^9,14 This is called hyperviscosity and can lead to problems such as bruising, nose bleeds, retinal bleeds, hazy vision, headaches, gastrointestinal bleeding, sleepiness, and a variety of ischemic neurological symptoms caused by reduced blood and oxygen supply to the nerve tissue.^8,14

In addition to hyperviscosity, thrombosis is another complication associated with multiple myeloma. Thrombosis, together with very low oxygen, may lead to coagulation-related complications.^8,20 Abnormal monoclonal proteins can bind to nerves to cause neuropathy or bind to circulating hormones to cause metabolic dysfunction.⁸

As you can see, the pathophysiology of multiple myeloma is complex. There are many clinical parameters that must be monitored to ensure safe and effective care of each patient. You can learn more about the important responsibility of managing these various complications by reviewing the complications section of the website.

This concludes the Multiple Myeloma Overview video. Be sure to explore this site for more informational videos and resources.

References

1. Pierre A, Williams TH. African American patients with multiple myeloma: optimizing care to decrease racial disparities. Clin J Oncol Nurs. 2020;24(4):439-443.

2. Cancer Facts & Figures 2021. American Cancer Society. 2021. Accessed August 31, 2021. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf

3. Cancer Stat Facts: Myeloma. National Cancer Institute: Surveillance, Epidemiology, and End Results (SEER) Program. Accessed August 31, 2021. https://seer.cancer.gov/statfacts/html/mulmy.html

4. Stoller R. 7 facts you need to know about blood cancers. National Foundation for Cancer Research. September 29, 2020. Accessed August 31, 2021. https://www.nfcr.org/blog/7-facts-need-know-blood-cancers/?gclid=CjwKCAjw8cCGBhB6EiwAgORey4DQSJSlm9SfSTFI%AD49WHLT0ab5q2lhs1qzJSaIi83JyoVBI6HnuHBoCaMkQAvD_BwE

5. Dhodapkar MV, Borrello I, Cohen AD, Stadtmauer EA. Hematologic malignancies: plasma cell disorders. Am Soc Clin Oncol Educ Book. 2017;37:561-568. doi:10.1200/EDBK_175546

6. Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. 5th ed. Garland Science; 2001.

7. About multiple myeloma. American Cancer Society. Updated February 28, 2018. Accessed August 31, 2021. https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf

8. Durie BGM. Concise review of the disease and treatment options: multiple myeloma. International Myeloma Foundation. 2018. Accessed August 31, 2021. https://imf-d8-prod.s3.us-west-1.wasabisys.com/resource/ConciseReview.pdf

9. Plasma cell neoplasms (including multiple myeloma) treatment (PDQ®)--health professional version. National Cancer Institute. Updated May 14, 2021. Accessed August 31, 2021. https://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq

10. Korde N, Kristinsson SY, Landgren O. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies. Blood. 2011;117(21):5573-81. doi:10.1182/blood-2011-01-270140

11. MGUS to myeloma: study suggests risk of progression can change. National Cancer Institute. August 13, 2019. Accessed August 31, 2021. https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk#:~:text=A%20new%20study%20suggests%20that,develop%20multiple%20myeloma%20each%20year

12. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-567. doi:10.1002/ajh.25791

13. Rajkumar SV. Updated diagnostic criteria and staging system for multiple myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418-23. doi: 10.1200/EDBK_159009

14. Albagoush SA, Azevedo AM. Multiple myeloma. National Center for Biotechnology Information. Updated July 30, 2021. Accessed August 31, 2021. https://www.ncbi.nlm.nih.gov/books/NBK534764/

15. Multiple myeloma and anemia. International Myeloma Foundation. Updated August 1, 2019. Accessed August 31, 2021. https://www.myeloma.org/multiple-myeloma-anemia

16. Early detection, diagnosis, and staging. American Cancer Society. Updated February 28, 2018. Accessed August 31, 2021. https://www.cancer.org/cancer/multiple-myeloma/detection-diagnosis-staging.html

17. Biran N, Jagannath S, Chari A. Risk stratification in multiple myeloma, part 1: characterization of high-risk disease. Clin Adv Hematol Oncol. 2013;11(8):489-503

18. Yang Y, Li Y, Gu H, Dong M, Cai Z. Emerging agents and regimens for multiple myeloma. J Hematol Oncol. 2020;13(1):150. doi:10.1186/s13045-020-00980-5

19. Landgren O, Iskander K. Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes. J Intern Med. 2017;281(4):365-382. doi:10.1111/joim.12590

20. Chakraborty R, Majhail NS. Treatment and disease-related complications in multiple myeloma: implications for survivorship. Am J Hematol. 2020;95(6):672-690. doi:10.1002/ajh.25764

21. Ludwig H, Delforge M, Facon T, et al. Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2018;32(7):1542-1560. doi:10.1038/s41375-018-0040-1