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Light Chain Multiple Myeloma: Your Ultimate Guide

Updated on April 20, 2020
Article written by
Jessica Wolpert

Light chain multiple myeloma is a type of multiple myeloma, a cancer of the plasma cells. Multiple myeloma begins in the bone marrow, where white blood cells are formed. When the body detects an infection, these white blood cells transform into plasma cells, which create proteins called immunoglobulins — also known as antibodies. These immunoglobulins, or Ig for short, work to eliminate dangerous bacteria and viruses. In people with multiple myeloma, plasma cells don’t work properly. Instead, they produce damaged Ig that harm the body. These damaged Ig are called monoclonal proteins, or M proteins.

Normal Ig are shaped like a Y, with four pieces linked together — two longer “heavy” chains and two shorter “light” chains. M proteins are excess quantities of one of these types of chains. About 20 percent of people with multiple myeloma are diagnosed with light chain multiple myeloma. People with light chain myeloma only produce the light chain component of abnormal immunoglobulins. These are also known as Bence-Jones proteins.

Symptoms of Light Chain Multiple Myeloma

Light chain multiple myeloma symptoms are similar to symptoms of other types of myeloma.

Bone Damage

Because multiple myeloma affects the bone marrow, about 85 percent of people with multiple myeloma will experience bone damage, often in the spine, pelvis, or ribs.

Gastrointestinal and Urinary Problems

Excess calcium from bone damage, called hypercalcemia, can cause urinary issues and gastrointestinal problems like stomach upset, excessive thirst, and diarrhea.

Neurological Symptoms

Hypercalcemia can also cause changes in mental state such as confusion and drowsiness.

Anemia

Myeloma’s effects on the bones can also cause anemia — a deficiency of red blood cells — and lowered immunity, as there are no longer enough normal white blood cells to fight infection. Anemia can cause fatigue and weakness.

Kidney Damage

One common effect of light chain multiple myeloma is kidney damage. The hypercalcemia associated with multiple myeloma can also damage the kidneys, but light chain variants of myeloma can be especially harmful. Because the light chains are so small, they easily circulate in the bloodstream. The kidneys contain tiny filters called glomeruli, which filter the blood and send waste materials into the urine. When excess light chains enter the glomeruli with the blood, they mix with other proteins and clog the filters. These clogs inflame and injure the kidney tissue. This damage is called light chain cast nephropathy. Over time, this buildup of light chains can cause permanent damage and kidney failure. Symptoms of kidney failure include urinary changes, fatigue, nausea, swollen feet and ankles, itching, shortness of breath, and high blood pressure.

Diagnosing Light Chain Multiple Myeloma

The tests used to detect light chain multiple myeloma are the same as those used to detect multiple myeloma generally. Your doctor might order the following tests:

Blood Tests

Blood tests can detect M proteins and other proteins that can indicate the aggressiveness of a multiple myeloma. Blood tests can also reveal low blood counts, poor kidney function, and high calcium levels.

Urine Tests

M proteins can be detected in the urine. Testing for M proteins usually involves collecting urine over a 24-hour period.

Bone Marrow Biopsy

Bone marrow cells are extracted through a long needle and examined in a laboratory for malignant cells.

Imaging

X-rays, magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT) scans can all show damage to the bones or to other organs caused by multiple myeloma.

Diagnostic Criteria for Light Chain Multiple Myeloma

Every diagnosis of light chain multiple myeloma begins with a general diagnosis of myeloma. There are two criteria for a diagnosis of multiple myeloma, according to the International Myeloma Working Group.

The first criterion is the detection of 10 percent or more malignant plasma cells in the bone marrow, or the detection of plasmacytoma in the bones or soft tissues. Plasmacytomas are tumors made up of malignant plasma cells.

The second criterion can be met in two ways. The first is the standard CRAB criteria. CRAB is an acronym for the types of damage that multiple myeloma can inflict on the body, including:

  • Calcium elevation.
  • Renal failure.
  • Anemia.
  • Bony lesions.

The CRAB criteria were the gold standard for multiple myeloma diagnosis for decades. However, with improved imaging technology and biomarker testing, multiple myeloma can now be diagnosed earlier, before it causes the damage that comprises the CRAB criteria. Along with the detection of malignant cells, these new criteria that confirm a diagnosis of multiple myeloma include:

  • 60 percent or more malignant plasma cells in a bone marrow biopsy.
  • Focal lesions of 5 millimeters or more. (A “focal lesion” is a small, defined injury.)
  • Serum free light chain ratio of 100 or more.

This last diagnostic criterion — a serum free light chain ratio of 100 or more — can be used to specifically diagnose light chain multiple myeloma. A blood test called the serum free light chain assay detects excess light chains in the blood. In people with light chain multiple myeloma, there will be a much higher level of kappa chains compared to lambda chains, or vice versa, because the M proteins are producing too much of one specific light chain.

Urine testing can also be helpful in detecting light chain myeloma caused by overproduction of lambda light chains. The urine protein electrophoresis test (UPEP) has been used in the past to detect light chain myeloma, but it has become less common due to expense. Light chain multiple myeloma is often diagnosed along with another condition called light chain amyloidosis (also called AL amyloidosis or primary amyloidosis). While multiple myeloma refers to the malignancies in the bone marrow, AL amyloidosis refers to the buildup of light chain proteins in the organs.

Treating Light Chain Multiple Myeloma

Most treatments for light chain multiple myeloma are similar to those for other forms of myeloma. Treating cases of light chain multiple myeloma can be complicated by the light chains’ tendency to cause kidney damage; 40 percent of people with multiple myeloma have kidney damage at the time of diagnosis.

Chemotherapy Drugs

For people with renal impairment, a chemotherapy drug called Velcade (Bortezomib) is usually prescribed as the first line of treatment. Velcade is a proteasome inhibitor. It works by “shutting off” the cell function that lets cells dispose of excess proteins. Because malignant myeloma cells produce too many proteins, they eventually “fill up” with these excess proteins and die. Velcade is administered through injections or infusions. Velcade is often combined with Dexamethasone, a type of corticosteroid. Corticosteroids are believed to help kill cancerous cells and can help ease side effects of chemotherapy drugs such as nausea and vomiting. A 2018 literature review found that Velcade is more effective at treating light chain multiple myeloma than other regimens.

High-Cutoff Hemodialysis

A type of kidney dialysis called high-cutoff hemodialysis (HCO-HD) is a newer treatment option for light chain multiple myeloma. HCO-HD is used alongside chemotherapy. Regular hemodialysis is used to help remove bodily waste that the injured kidneys can no longer remove. During HCO-HD, the blood is purified through a special membrane which is designed to trap excess light chain proteins.

Small studies have shown that high-cutoff hemodialysis may help improve kidney function in people with light chain multiple myeloma. HCO-HD is still new, and additional research is required to understand the full range of its benefits and risks.

Plasmapheresis

Plasmapheresis, also known as blood exchange, can also be used to remove light chains and support chemotherapy treatment. During plasmapheresis, the liquid component of the blood is removed and replaced with plasma from a donor or with a plasma substitute. The process is usually done in a medical center or a hospital, and it takes about two to three hours.

On MyMyelomaTeam, the social network and online support group for those living with myeloma, members talk about a range of personal experiences, including light chain multiple myeloma.

Here are a few question-and-answer threads about light chain multiple myeloma and its treatments:

Here are some conversations about light chain multiple myeloma:

Do you have light chain multiple myeloma? Share your experience in the comments below or on MyMyelomaTeam. You'll be surprised how many others share similar stories.

FAQ

Are there other subtypes of myeloma besides kappa and lambda?
Kappa and lambda are the only two subtypes of light chain multiple myeloma. However, sometimes the body produces too many heavy chains, which also causes multiple myeloma. There are five different types of these heavy chain proteins: IgG, IgA, IgD, IgE, and IgM. IgG overproduction is the most common type of heavy chain multiple myeloma, followed by IgA. IgD-related multiple myeloma is much less common, as is IgE multiple myeloma. Overproduction of IgM is usually associated with rare lymph node conditions, not with the bone marrow involved in multiple myeloma.

Compared to light chain multiple myeloma, these types of multiple myelomas are easier to detect in the blood since the heavier proteins aren’t filtered out through the kidneys and into the urine.

References

  1. What Is Multiple Myeloma? — American Cancer Society
  2. Understanding Multiple Myeloma and Laboratory Values — Gunderson Health System Center for Cancer and Blood Disorders
  3. Types of Myeloma — Cancer Research UK
  4. Symptoms, Side Effects, and Complications — Multiple Myeloma Research Foundation
  5. Signs and Symptoms of Multiple Myeloma — American Cancer Society
  6. Myeloma Kidney — UNC Kidney Center
  7. Light Chain Cast Neuropathy — American Journal of Kidney Diseases
  8. Tests to Find Multiple Myeloma — American Cancer Society
  9. About Multiple Myeloma — UCSF Helen Diller Family Comprehensive Cancer Center
  10. International Myeloma Working Group (IMWG) criteria for the diagnosis of multiple myeloma — International Myeloma Foundation
  11. Serum free light-chain assay for the detection and monitoring of multiple myeloma and related conditions — Therapeutic Advances in Hematology
  12. Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies — Journal of Clinical Medicine Research
  13. Amyloidosis Types — Stanford Health Care
  14. Paraprotein–Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy — CJASN
  15. Extracorporeal Removal of Light Chains: New Data and Continued Controversies — CJASN
  16. Proteasome Inhibitors — Multiple Myeloma Research Foundation
  17. An Overview of Light Chain Multiple Myeloma: Clinical Characteristics and Rarities, Management Strategies, and Disease Monitoring — Cureus
  18. Supportive Treatments for Patients with Multiple Myeloma — American Cancer Society
  19. Plasmapherisis Patient Handout — UC San Diego Health System
  20. Types of Multiple Myeloma — Canadian Cancer Society

Jessica works to empower patients through the creation of content that illuminates treatments' effects on the everyday lives of people with chronic conditions. Learn more about her here.

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