Types of Multiple Myeloma

Multiple myeloma is a blood cancer that develops when abnormal plasma cells multiply in the bone marrow. Although all multiple myelomas originate from plasma cells, the disease can be classified in several ways, including by the type of abnormal immunoglobulin, or antibody, the myeloma cells produce and by the genetic characteristics of those cells.

Identifying these features can provide important information about how the disease can be measured, how it may behave and which treatments may be appropriate. For this reason, a precise diagnosis involves more than confirming the presence of multiple myeloma; it also requires detailed laboratory and molecular characterization of the cancer.

IgG multiple myeloma

IgG multiple myeloma is the most common immunoglobulin-defined form of the disease. It develops when a clone of malignant plasma cells produces an abnormal monoclonal immunoglobulin G (IgG) protein.

Like other complete immunoglobulins, IgG consists of heavy chains paired with light chains. Therefore, IgG myeloma can be further described as IgG kappa or IgG lambda, depending on which light chain the cancerous plasma cells produce.

IgG myeloma generally causes the same potential manifestations as multiple myeloma overall, such as bone damage, anemia, kidney problems, high blood calcium levels and increased susceptibility to infection. The IgG M-protein also provides a measurable marker that the healthcare team can follow with blood testing to assess the disease and its response to treatment.

An IgG designation alone does not determine whether myeloma is considered standard or high risk. Cytogenetic abnormalities, disease stage, laboratory findings, the patient’s overall health and other characteristics can provide additional information that helps guide treatment.

IgA multiple myeloma

IgA multiple myeloma is the second-most common immunoglobulin-defined type of myeloma. In this form, malignant plasma cells produce an abnormal immunoglobulin A (IgA) protein, which can contain either kappa or lambda light chains. IgA myeloma can affect the bones, bone marrow, kidneys and other parts of the body in much the same way as other forms of multiple myeloma.

Laboratory testing can identify and quantify the IgA monoclonal protein, while bone marrow testing and cytogenetic studies can provide additional information about the cancer. Treatment is not selected solely on the basis of the IgA protein. Instead, the healthcare team will consider the complete biological and clinical profile of the myeloma when developing a treatment plan.

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Light chain multiple myeloma

Light chain multiple myeloma, also called Bence Jones myeloma, occurs when cancerous plasma cells produce only one component of an immunoglobulin rather than a complete antibody. The abnormal cells produce either kappa light chains or lambda light chains. Because free light chains are relatively small proteins, they can pass from the bloodstream into the kidneys, where excessive amounts can cause kidney damage.

Light chain myeloma also requires a somewhat different approach to laboratory monitoring because a conventional serum protein electrophoresis test may not adequately reflect the amount of disease. Serum free light chain testing, along with urine studies and other assessments, can help the healthcare team diagnose and monitor this form of myeloma.

Treatment generally draws from the same major therapies used for other forms of active multiple myeloma, but the patient’s kidney function, cytogenetic risk and other disease characteristics can affect the specific regimen and supportive care plan.

Nonsecretory multiple myeloma

Nonsecretory multiple myeloma is an uncommon form of the disease in which the malignant plasma cells produce little or no monoclonal protein detectable in the blood or urine with conventional protein testing. Only a small percentage of patients with multiple myeloma have truly nonsecretory disease.

The absence of a readily measurable M-protein can make this form of myeloma more challenging to diagnose and monitor. The patient may still have abnormal plasma cells in the bone marrow, bone lesions or other evidence of myeloma despite having negative or minimally abnormal conventional protein studies.

Bone marrow examination and imaging therefore play a particularly important role in evaluating nonsecretory myeloma. Serum free light chain testing can also be informative for some patients whose disease produces small quantities of light chains that are not apparent on standard protein electrophoresis.

Nonsecretory myeloma is generally treated using the same classes of therapies as secretory multiple myeloma. Physicians may rely more heavily on bone marrow findings, imaging and other disease markers to determine whether treatment is working.

Other rare types of multiple myeloma

Several immunoglobulin-defined forms of multiple myeloma occur much less frequently than IgG, IgA and light chain myeloma. These include:

• IgD multiple myeloma – In this rare form, malignant plasma cells produce an IgD monoclonal protein. Because the amount of circulating M-protein may be relatively low, serum free light chain testing and other studies can be particularly important during the diagnostic evaluation.
• IgE multiple myeloma – IgE myeloma is exceptionally rare and is defined by production of a monoclonal IgE protein. Its rarity makes an evaluation by a specialist familiar with unusual plasma cell disorders particularly valuable.
• IgM multiple myeloma – This form of myeloma is also very rare. An IgM monoclonal protein is much more commonly associated with Waldenström macroglobulinemia, a different type of blood cancer, so careful hematopathologic and molecular evaluation is important to distinguish between these diseases.
• Biclonal multiple myeloma – Rarely, testing identifies two distinct monoclonal proteins rather than one. Additional laboratory and bone marrow evaluation can help characterize the abnormal plasma cell populations and establish the diagnosis.

Moffitt Cancer Center’s hematopathologists and multiple myeloma specialists have access to advanced laboratory, molecular and imaging capabilities that can be especially valuable when evaluating an unusual or diagnostically complex plasma cell disorder.

How the types of multiple myeloma are diagnosed

Determining the type of multiple myeloma requires several complementary tests. Unlike many solid tumors, myeloma is not classified primarily according to the tissue layer where the cancer originated. Instead, the healthcare team will evaluate the proteins produced by the abnormal plasma cells, examine the cells in the bone marrow and analyze their genetic characteristics.

The diagnostic evaluation for multiple myeloma may include:

• Blood and urine protein studies – Serum protein electrophoresis (SPEP) can detect and measure an M-protein in the blood, while immunofixation can help identify its specific heavy- and light-chain type. Urine protein electrophoresis (UPEP) and urine immunofixation can detect monoclonal proteins, including light chains, excreted in the urine.
• Quantitative immunoglobulin testing – This blood test measures the levels of the major immunoglobulin classes, including IgG, IgA and IgM, providing additional information about the monoclonal protein and the function of normal antibodies.
• Serum free light chain testing – This test measures free kappa and lambda light chains and calculates the ratio between them. It is particularly useful when evaluating light chain myeloma and some forms of myeloma with little or no M-protein detectable through conventional electrophoresis.
• Bone marrow aspiration and biopsy – A sample of bone marrow can be examined by a hematopathologist to determine the percentage and characteristics of abnormal plasma cells. Specialized testing, including immunophenotyping or flow cytometry, can provide additional information about the plasma cell population.
• Cytogenetic and molecular testing – Fluorescence in situ hybridization (FISH) and other techniques can identify chromosomal abnormalities within myeloma cells. Findings such as certain translocations, chromosome 17p abnormalities and changes involving chromosome 1 can help the healthcare team assess biological risk and may influence treatment decisions.
• Imaging studies – Low-dose whole-body CT, PET/CT or MRI may be used to look for bone lesions, focal bone marrow abnormalities or disease outside the bone marrow. Imaging does not usually determine the immunoglobulin type, but it can provide important information about the extent and activity of the disease.

The findings of these tests will be interpreted together. Two patients may both have IgG myeloma, for example, while having substantially different cytogenetic features, disease burdens and clinical characteristics that affect prognosis and treatment planning.

Frequently asked questions (FAQs) about the types of multiple myeloma 

Multiple myeloma can be described in several different ways, which can make the terms used in a pathology or laboratory report difficult to interpret. The following answers explain some of the classifications the patient may encounter.

What is the difference between active multiple myeloma and smoldering multiple myeloma?

Smoldering multiple myeloma is an asymptomatic plasma cell disorder in which abnormal plasma cells or monoclonal protein levels meet defined thresholds, but the patient does not have myeloma-defining events that establish active disease. Smoldering myeloma generally requires close monitoring, with the frequency and management approach based on the patient’s individual risk

Active multiple myeloma meets established diagnostic criteria indicating that the disease is causing organ damage or has specific biomarkers associated with a sufficiently high risk of progression. Active myeloma generally requires treatment, while many patients with smoldering myeloma are initially monitored rather than treated.

What do the different immunoglobulin types, such as IgG or IgA myeloma, mean?

A designation of IgG or IgA identifies the type of monoclonal immunoglobulin produced by the cancerous plasma cells. For example, IgG myeloma produces an abnormal IgG protein, while IgA myeloma produces an abnormal IgA protein.

The complete designation may also identify the light chain, such as IgG kappa or IgA lambda. These protein types can help the healthcare team characterize and monitor the disease, but they are only part of the information used to assess the prognosis and select treatment.

What is light chain multiple myeloma?

Light chain multiple myeloma occurs when malignant plasma cells produce only kappa or lambda light chains instead of a complete immunoglobulin. Because excessive free light chains can damage the kidneys, renal function will be closely monitored and serum free light chain testing will play an important role in evaluating the disease.

What is nonsecretory multiple myeloma?

Nonsecretory multiple myeloma produces little or no monoclonal protein detectable by conventional blood or urine protein testing. As a result, the healthcare team may rely more heavily on bone marrow examination, imaging, serum free light chain testing (when informative) and other clinical findings to diagnose and monitor the disease.

How do cytogenetics affect the classification of multiple myeloma?

Cytogenetic testing examines the chromosomes of myeloma cells for abnormalities that can provide information about the cancer’s biology and expected behavior. FISH testing can identify changes such as translocations, deletions and gains or amplifications of chromosome material that can help the healthcare team classify myeloma into biological risk groups.

These findings can be clinically important because some abnormalities are associated with more aggressive disease or may influence the selection or duration of certain therapies. Cytogenetic results are therefore interpreted alongside the patient’s cancer stage, laboratory findings, overall health and response to treatment rather than being considered in isolation.

Are IgG and IgA myeloma treated differently?

Not necessarily. The immunoglobulin type can help characterize and monitor multiple myeloma, but treatment decisions are based on a broader range of factors, including whether the disease is active and its cytogenetic risk profile as well as the patient’s kidney function, overall health, prior therapies and candidacy for bone marrow transplantation.

Can the type of multiple myeloma change?

The monoclonal protein produced by myeloma often remains consistent, but the biological characteristics of the cancer can evolve over time as different plasma cell clones acquire or lose genetic abnormalities. For this reason, the healthcare team may repeat certain laboratory, bone marrow or molecular tests if multiple myeloma relapses or begins behaving differently.

The Moffitt Cancer Center approach to multiple myeloma

Precisely characterizing multiple myeloma can provide information that extends well beyond the name of the disease. At Moffitt, patients have access to specialists in the Malignant Hematology Program who focus on blood cancers such as multiple myeloma and work with hematopathologists, radiologists, transplant specialists, radiation oncologists and other experts to evaluate each patient’s disease from multiple perspectives.

Moffitt's specialized pathology capabilities include hematopathology, flow cytometry, immunohistochemistry and molecular diagnostics. For a patient who has already received a multiple myeloma diagnosis elsewhere, seeking a second opinion at Moffitt can provide an opportunity for specialists to review the original diagnostic findings, perform additional testing when appropriate and confirm the precise characteristics of the disease. This detailed evaluation can reduce the risk of an incomplete or incorrect classification and provide a strong foundation for an individualized treatment plan.

Moffitt also brings specialists together through a multispecialty approach to care. Depending on the patient’s needs, treatment may incorporate a combination of targeted therapy, immunotherapy, chemotherapy, bone marrow transplantation, CAR T-cell therapy or other approaches. Eligible patients may also have opportunities to participate in clinical trials evaluating promising new strategies for multiple myeloma.

As a National Cancer Institute (NCI)-designated Comprehensive Cancer Center and a high-volume center for malignant hematologic diseases, Moffitt combines specialized clinical care with research aimed at improving the diagnosis and treatment of multiple myeloma.

To learn more about the types of multiple myeloma, you can request an appointment with a specialist in Moffitt’s Malignant Hematology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.