Myeloma Terminology

A type of blood cancer that affects plasma cells in the bone marrow. These abnormal plasma cells multiply uncontrollably and can crowd out healthy blood cells, leading to various complications. The disease interferes with normal antibody production, weakens bones, and can affect kidney function. Treatment has advanced significantly with many patients living years with good quality of life through modern therapies.

White blood cells that produce antibodies to help fight infections. In multiple myeloma, these cells become cancerous and produce abnormal proteins instead of helpful antibodies. Normal plasma cells make up less than 5% of bone marrow, but in myeloma, cancerous plasma cells can make up 10% or more. These cells are mature B lymphocytes that have specialized in antibody production.

The soft, spongy tissue inside bones where blood cells are made. This is where myeloma cells grow and multiply, crowding out healthy blood-producing cells. Bone marrow produces red blood cells (carry oxygen), white blood cells (fight infection), and platelets (help blood clot). A bone marrow biopsy is essential for diagnosing myeloma and determining the percentage of cancerous plasma cells present.

An abnormal protein produced by myeloma cells, also called paraprotein. It can be detected in blood or urine tests and is used to monitor the disease activity and response to treatment. The level of M protein typically correlates with the amount of myeloma present in the body. Tracking M protein levels over time helps doctors assess how well treatment is working and detect early signs of relapse.

Parts of antibodies that can be produced in excess by myeloma cells. Free light chains in blood or urine can indicate disease activity, especially in patients who don't produce measurable M protein. There are two types: kappa and lambda. The ratio between these two types helps doctors monitor disease. High levels of free light chains can damage kidneys and are measured through the serum free light chain assay.

High levels of calcium in the blood, often caused by bone destruction from myeloma. Can cause fatigue, confusion, excessive thirst, frequent urination, constipation, and kidney problems. This occurs when calcium is released from damaged bones into the bloodstream faster than kidneys can eliminate it. Treated with hydration, medications like bisphosphonates, and addressing the underlying myeloma. It's the 'C' in CRAB criteria.

Low red blood cell count, common in myeloma patients when cancerous plasma cells crowd out red blood cell production in bone marrow. Causes fatigue, weakness, shortness of breath, dizziness, and pale skin. It's the 'A' in CRAB criteria. May be treated with blood transfusions, medications like erythropoietin, or by treating the underlying myeloma effectively. Hemoglobin levels below 10 g/dL indicate significant anemia.

Kidney problems that can occur in myeloma patients due to high protein levels (light chains), elevated calcium, dehydration, or certain medications. Light chains can damage kidney tubules, while high calcium can cause calcium deposits in kidneys. It's the 'R' in CRAB criteria. Early detection and aggressive hydration are crucial. Some patients may need dialysis, though kidney function often improves with effective myeloma treatment.

Areas of bone damage or 'holes' caused by myeloma cells destroying bone tissue. Can cause pain, fractures, and spinal cord compression. These appear as dark spots on X-rays or CT scans. It's the 'B' in CRAB criteria. Myeloma cells activate osteoclasts (cells that break down bone) while suppressing osteoblasts (cells that build bone). Treated with bisphosphonates or denosumab to strengthen bones and prevent complications.

The main complications of myeloma used to determine if treatment is needed: Calcium elevation (hypercalcemia), Renal impairment (kidney problems), Anemia (low red blood cells), and Bone lesions (bone damage). The presence of any CRAB symptom, along with evidence of myeloma cells, indicates active myeloma requiring treatment. Modern criteria also include biomarkers like bone marrow plasma cells ≥60% or involved/uninvolved free light chain ratio ≥100.

A procedure to remove a small sample of bone marrow tissue, usually from the hip bone, to examine for myeloma cells and determine the percentage present. Performed under local anesthesia, the test provides crucial information for diagnosis, staging, and monitoring response to treatment. The sample is analyzed to look at cell types, genetic abnormalities, and plasma cell percentage. While uncomfortable, it's essential for accurate myeloma diagnosis and treatment planning.

A blood test that separates proteins by their electrical charge to detect abnormal proteins (M protein) produced by myeloma cells. Creates a pattern showing different protein bands, with myeloma often showing a characteristic 'spike' or 'M spike'. Used for initial diagnosis and ongoing monitoring. The size of the M spike generally correlates with disease burden. This test is done regularly to track treatment response and detect relapse early.

A urine test to detect abnormal proteins, particularly light chains (Bence Jones protein), that may indicate myeloma. Requires a 24-hour urine collection for accurate measurement. Important because some myeloma patients produce only light chains without a full M protein. High levels of urinary light chains can damage kidneys. Used alongside blood tests for complete disease monitoring, especially in light chain myeloma.

A more sensitive test than protein electrophoresis to identify and characterize the specific type of abnormal protein (IgG, IgA, IgM, or light chain only). Can detect small amounts of M protein that might be missed by standard electrophoresis. Performed on both blood and urine samples. Helps classify the type of myeloma and is particularly useful for detecting minimal residual disease after treatment. Essential for confirming complete response.

A blood test that measures the levels of free kappa and lambda light chains to monitor disease activity. More sensitive than urine tests for detecting light chains. The ratio between kappa and lambda (normal is 0.26-1.65) is particularly important. Abnormal ratios indicate clonal plasma cell production. Especially valuable for monitoring light chain and non-secretory myeloma. Results can change rapidly with treatment, making it useful for early assessment of response.

A protein found on cell surfaces that's released into blood. High levels can indicate more advanced myeloma, larger tumor burden, and reduced kidney function. It's a key component of the International Staging System (ISS) for myeloma: Stage I (<3.5 mg/L), Stage II (3.5-5.5 mg/L), Stage III (>5.5 mg/L). Combined with albumin levels and genetic markers to predict prognosis. Levels typically decrease with successful treatment.

An enzyme that can be elevated when cells are damaged or destroyed, often raised in active or aggressive myeloma. Found in nearly all body tissues but particularly high in rapidly dividing cells. Very high LDH levels may indicate plasma cell leukemia or more aggressive disease. Part of the Revised-ISS staging system. Not specific to myeloma but provides important information about disease activity and prognosis when elevated.

Testing to examine chromosomes in myeloma cells to identify genetic abnormalities that affect prognosis and treatment. Standard karyotyping looks at chromosomes under a microscope to detect large-scale changes. Can identify high-risk features like deletion 17p, t(4;14), t(14;16), or gain of 1q. Results help doctors choose appropriate treatment intensity and predict likely disease course. Important for risk stratification and personalized treatment planning.

A genetic test that uses fluorescent probes to look for specific chromosome changes in myeloma cells. More sensitive than standard cytogenetics, especially for detecting abnormalities in non-dividing cells. Can identify high-risk genetic features like deletion 17p, t(4;14), t(14;16), t(14;20), and gain/amplification of 1q21. Results guide treatment decisions, with high-risk genetics often requiring more intensive therapy. Performed on bone marrow samples at diagnosis and sometimes at relapse.

The first treatment given to reduce the number of myeloma cells and achieve remission. Usually consists of 3-4 drug combinations given over 4-6 cycles (each cycle is typically 3-4 weeks). Common regimens include combinations of proteasome inhibitors, immunomodulatory drugs, and steroids. The goal is to achieve the deepest response possible before moving to consolidation or transplant. Response is measured by reduction in M protein levels and bone marrow plasma cells.

Treatment given after induction to further reduce myeloma cells and deepen response. Often includes autologous stem cell transplant for eligible patients, though this timing is debated. May also involve additional cycles of chemotherapy or different drug combinations. The goal is to eliminate as many remaining myeloma cells as possible. Decisions about consolidation depend on age, fitness, disease characteristics, and response to induction therapy.

Long-term treatment given after initial therapy to keep myeloma in remission for as long as possible. Usually involves single drugs like lenalidomide or bortezomib at lower doses than induction. Continued indefinitely or until progression or unacceptable toxicity. Studies show maintenance significantly extends progression-free survival. The duration and choice of maintenance drug depends on prior treatments, risk factors, side effects, and patient preference.

A procedure using the patient's own stem cells to restore bone marrow after high-dose chemotherapy (usually melphalan). Stem cells are collected before intensive chemo, frozen, then returned after treatment to rebuild the immune system. Not a cure but significantly extends remission. Standard of care for fit, newly diagnosed patients under 70-75 years. Recovery takes 2-3 weeks in hospital plus several months at home. Can be repeated if first transplant was successful.

A procedure using stem cells from a matched donor (sibling or unrelated) to replace the patient's bone marrow. Rarely used for myeloma due to high treatment-related mortality (15-30%) and severe graft-versus-host disease risk. The donor's immune cells can attack remaining myeloma (graft-versus-myeloma effect) but also attack normal tissues. Mostly reserved for younger patients with very aggressive disease in research settings. Non-myeloablative (mini) transplants are being studied as safer alternatives.

The process of moving stem cells from bone marrow into the bloodstream for collection before transplant. Achieved using growth factors (G-CSF/filgrastim) alone or combined with chemotherapy or plerixafor. Takes 4-5 days of injections, followed by 1-2 days of collection via apheresis (similar to dialysis). Goal is to collect 2-4 million CD34+ cells per kg of body weight. Poor mobilizers may need additional medications or procedures. Collected cells are frozen until needed for transplant.

High-dose chemotherapy given before stem cell transplant to destroy myeloma cells and make room for new stem cells. For myeloma, typically high-dose melphalan (140-200 mg/m²). Given 1-2 days before stem cell infusion. Causes temporary but severe drop in blood counts, requiring hospitalization and supportive care. Side effects include mouth sores, nausea, fatigue, and increased infection risk. The intensity can be adjusted based on age, kidney function, and overall health.

When transplanted stem cells begin to grow and produce new blood cells in the bone marrow. Usually occurs 10-14 days after stem cell infusion. Marked by rising white blood cell counts, first neutrophils then platelets. Patients remain hospitalized during this vulnerable period, receiving antibiotics, transfusions, and growth factors. Once counts recover sufficiently (usually neutrophils >500), patients can go home. Full immune recovery takes 3-6 months or longer. Failure to engraft is rare but requires urgent intervention.

An immunomodulatory drug (IMiD) that enhances the immune system's ability to fight myeloma cells and has anti-angiogenic properties. Works through multiple mechanisms including activating T-cells and NK cells, inhibiting blood vessel formation, and directly causing myeloma cell death. Taken orally as a pill, usually with dexamethasone. Common in induction regimens (VRd, RVd) and standard for maintenance therapy. Side effects include low blood counts, increased blood clot risk, fatigue, and rash. Requires monitoring and pregnancy prevention measures.

A proteasome inhibitor that blocks proteins needed for myeloma cell survival, causing cell death. The first proteasome inhibitor approved for myeloma, revolutionizing treatment. Given by subcutaneous injection (under the skin) or IV, usually twice weekly. Key component of many regimens like VRd (bortezomib-lenalidomide-dexamethasone) and CyBorD. Main side effect is peripheral neuropathy (nerve damage causing numbness/tingling), though subcutaneous dosing reduces this risk. Other effects include low platelet counts, fatigue, and gastrointestinal issues.

A newer, more potent proteasome inhibitor, often used when bortezomib is no longer effective or causes too much neuropathy. Given intravenously, typically on days 1, 2, 8, 9, 15, 16 of a 28-day cycle. Has less neuropathy than bortezomib but can affect the heart and lungs, requiring cardiac monitoring. Often combined with dexamethasone (Kd regimen) or lenalidomide-dexamethasone (KRd). Effective in relapsed/refractory myeloma with response rates of 50-70% in combination regimens.

A powerful corticosteroid with direct anti-myeloma effects, often combined with other treatments to enhance their effectiveness. Works by triggering myeloma cell death and reducing inflammation. Given as pills or IV infusion. Doses vary widely from low-dose (20-40mg weekly) to high-dose (40mg days 1-4 weekly). Common side effects include insomnia, increased appetite/weight gain, mood changes, high blood sugar, and increased infection risk. Long-term use can weaken bones and cause muscle weakness. An essential component of most myeloma regimens.

A monoclonal antibody that targets CD38 protein highly expressed on myeloma cells, helping the immune system attack them. Given by IV infusion (first dose takes 6-8 hours) or subcutaneous injection (3-5 minutes). Now standard in frontline therapy combined with VRd or other regimens. Also effective in relapsed disease. Common side effects include infusion reactions (reduced with subcutaneous), low blood counts, fatigue, and increased respiratory infections. Can interfere with blood typing tests. Response rates of 80-90% when combined with standard regimens.

A monoclonal antibody that targets SLAMF7 protein to enhance immune system recognition of myeloma cells. Works by both directly activating NK cells and marking myeloma cells for destruction. Given by IV infusion, typically with lenalidomide and dexamethasone. Approved for relapsed/refractory myeloma after 1-3 prior therapies. Infusion reactions are common with first doses. Generally well-tolerated with side effects mainly from combination partners. Response rates of 60-80% in combination with lenalidomide-dexamethasone in relapsed patients.

An immunomodulatory drug similar to but more potent than lenalidomide, often used in relapsed/refractory myeloma when lenalidomide stops working. Taken orally, typically combined with dexamethasone and often with daratumumab or elotuzumab. Effective even in lenalidomide-refractory disease with response rates of 30-65% depending on combination. Side effects include low blood counts (especially neutropenia), fatigue, infections, and increased blood clot risk. Requires the same pregnancy prevention program as lenalidomide. Usually given 21 days on, 7 days off in 28-day cycles.

The first oral proteasome inhibitor that can be taken at home as a pill, unlike IV proteasome inhibitors like bortezomib and carfilzomib. Given weekly (days 1, 8, 15 of 28-day cycle) with lenalidomide-dexamethasone. Causes less neuropathy than bortezomib. Convenient oral administration improves quality of life. Approved for relapsed myeloma after 1-3 prior therapies. Side effects include diarrhea, low platelets, nausea, and rash. Response rates of 70-80% in combination with lenalidomide-dexamethasone. Sometimes used in maintenance therapy.

A histone deacetylase (HDAC) inhibitor used in combination with bortezomib and dexamethasone for relapsed myeloma after 2+ prior regimens. Works by altering gene expression in myeloma cells, making them more susceptible to other treatments. Given orally three times per week. Has significant side effects including diarrhea, fatigue, low blood counts, nausea, and heart rhythm changes requiring ECG monitoring. Reserved for patients who have exhausted other options. Response rates around 60% in combination therapy.

A chemotherapy drug (alkylating agent) often used in high doses (140-200 mg/m²) before stem cell transplant as the conditioning regimen. At lower doses, used in combination regimens or as oral therapy. Has been a cornerstone of myeloma treatment for decades. High-dose melphalan is toxic to bone marrow, requiring stem cell rescue. Dose adjusted for age and kidney function. Side effects include severe but temporary bone marrow suppression, mouth sores, nausea, and hair loss. Increases risk of second cancers with long-term use.

A chemotherapy drug (alkylating agent) used in combination regimens for myeloma treatment like CyBorD (cyclophosphamide-bortezomib-dexamethasone). Also used for stem cell mobilization to help move stem cells into bloodstream for collection. Given orally or IV depending on purpose and dose. Generally well-tolerated at myeloma doses. Side effects include low blood counts, bladder irritation (requires hydration), nausea, and hair thinning. Can affect fertility. Effective in renal impairment when other drugs need dose reduction.

A selective inhibitor of nuclear export (SINE) that forces myeloma cells to keep tumor suppressor proteins in the nucleus where they can trigger cell death. Given orally twice weekly with dexamethasone. Approved for heavily pre-treated relapsed/refractory myeloma (4+ prior therapies including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies). Significant side effects include nausea, fatigue, decreased appetite, weight loss, low blood counts, and low sodium. Requires careful monitoring and supportive medications. Response rates 25-30% in heavily pre-treated patients.

An antibody-drug conjugate that delivers chemotherapy directly to myeloma cells through the BCMA (B-cell maturation antigen) target found on plasma cells. Given by IV infusion every 3 weeks. Approved for relapsed/refractory myeloma after 4+ prior therapies. Main concern is eye toxicity (keratopathy) requiring regular eye exams and sometimes dose delays or reductions. Other side effects include low blood counts and infusion reactions. Response rates 30-35% as single agent in heavily pre-treated patients. Currently being studied in earlier treatment lines and combinations.

A treatment that modifies the patient's own T-cells to better recognize and attack myeloma cells expressing BCMA protein. Two FDA-approved options: idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti). Requires collection of T-cells via apheresis, genetic modification in lab (2-4 weeks), then infusion back to patient after chemotherapy. Can produce dramatic responses (70-98%) including complete remissions in heavily pre-treated patients. Risks include cytokine release syndrome and neurotoxicity. Approved after 4+ prior therapies; studies ongoing in earlier lines. Single infusion can provide long-lasting remissions.

Drugs like zoledronic acid (Zometa) or pamidronate used to strengthen bones and reduce bone complications in myeloma. Work by inhibiting osteoclasts (cells that break down bone), reducing fractures, pain, and hypercalcemia. Given by IV infusion monthly, or zoledronic acid can be given every 3 months after initial period. Denosumab (Xgeva) is an alternative given as subcutaneous injection. Important side effect is osteonecrosis of the jaw (ONJ), requiring good dental care and preventive measures. Can affect kidney function. Continued throughout myeloma treatment and remission.

A bispecific T-cell engager antibody that targets GPRC5D protein on myeloma cells. Approved for relapsed/refractory multiple myeloma after four or more prior treatments. Works by linking T-cells to myeloma cells, helping the immune system attack cancer. Shows strong response rates (70-80%) in heavily pre-treated patients with common side effects including cytokine release syndrome, infections, and taste changes.