Multiple Myeloma: Symptoms, Types, Causes and Treatment

Multiple myeloma is a complex and challenging blood cancer that affects thousands of people worldwide each year. Understanding its symptoms, the different types, underlying causes, and the evolving landscape of treatments is essential for patients, caregivers, and healthcare professionals alike. In this article, we provide a comprehensive, evidence-based overview of multiple myeloma, synthesizing current research to help you better understand this disease and its management.

Symptoms of Multiple Myeloma

Multiple myeloma doesn’t always announce itself loudly at first. Early symptoms are often subtle, and many people are diagnosed incidentally during routine blood tests. However, as the disease progresses, the symptom burden grows significantly, often impacting quality of life. Recognizing these symptoms early can lead to faster diagnosis and better management.

Symptom	Description	Prevalence/Impact	Source(s)
Bone pain	Persistent pain (often back or ribs)	Up to 72% of patients	1 3 4 5
Fatigue	Tiredness not relieved by rest	55–88%	3 4 5
Anemia	Low red blood cells, causing weakness	Common	1 3 10
Renal issues	Kidney dysfunction/failure	Frequent complication	1 10
Hypercalcemia	High blood calcium levels	Can be severe	1 6 10
Infections	Recurring bacterial/viral infections	Increased risk	1 9 10
Worry/Anxiety	Mental distress, core symptom on chemo	Highly prevalent	4 5
Mobility loss	Difficulty moving/walking	Significant impact	4

Table 1: Key Symptoms of Multiple Myeloma

Common Symptoms and Their Impact

Multiple myeloma typically presents with a combination of physical and emotional symptoms, many of which overlap with other conditions. The most recognized features can be remembered with the acronym “CRAB”:

• Calcium elevation (hypercalcemia)
• Renal insufficiency
• Anemia
• Bone pain or lesions

Bone pain is the most frequent symptom, often affecting the back and ribs. This pain is due to the destructive effect of malignant plasma cells on bone tissue, leading to fractures and skeletal complications 1 3 11. Fatigue is also extremely common, and is often a result of anemia or the side effects of treatment 3 4 5.

Emotional and Quality of Life Concerns

Beyond physical symptoms, patients often report high levels of worry and anxiety. This psychological burden is particularly pronounced during chemotherapy, where “worrying” has been identified as a core symptom that influences and is influenced by other symptoms such as pain, nausea, and vomiting 4 5. Quality of life is further reduced by loss of mobility, sleeping problems, and nutritional issues.

Complications and Disease Progression

As the disease advances, complications such as kidney dysfunction (from light chain deposition), hypercalcemia (from bone destruction), and increased risk of infection (due to immune suppression) become prominent 1 9 10. These complications can be life-threatening without timely intervention.

Recognizing the Full Spectrum

It’s important to note that symptom burden varies greatly between individuals and disease stages. Some patients experience only mild symptoms for years, while others develop severe complications rapidly. Regular symptom monitoring, including patient-reported outcomes, is crucial for tailored supportive and palliative care 3 4.

Types of Multiple Myeloma

Multiple myeloma is not a single disease but a spectrum of related disorders. Understanding the different types is important because they influence prognosis, monitoring, and treatment strategies.

Type / Subtype	Key Feature(s)	Prevalence/Notes	Source(s)
Secretory MM	Produces monoclonal protein	Most common (majority of cases)	1 8 10
Non-secretory MM	Lacks detectable M-protein	~1–2% of cases	8
Smoldering MM (SMM)	Asymptomatic, no organ damage	Precursor to active MM	1 7 10 11
MGUS	Benign, stable plasma cell clone	Precursor state, low risk	1 7 11
Solitary Plasmacytoma	Single bone or soft tissue site	Localized, not full MM	7 10
Light Chain MM	Only light chains produced	Variable risk	10
Subtypes by Genetics	Hyperdiploid & Nonhyperdiploid	Prognosis varies by genetics	6 7 16

Table 2: Types and Subtypes of Multiple Myeloma

Classic (Secretory) Multiple Myeloma

This is the typical form, where malignant plasma cells secrete abnormal immunoglobulin (M-protein) detectable in blood or urine. This protein is a hallmark for diagnosis and monitoring 1 10.

Non-Secretory Multiple Myeloma

A rare type (~1–2% of cases), non-secretory MM does not produce detectable M-protein, making diagnosis and monitoring more challenging. Patients are diagnosed based on bone marrow and imaging findings 8.

Smoldering Multiple Myeloma (SMM) and MGUS

Smoldering MM and Monoclonal Gammopathy of Undetermined Significance (MGUS) are asymptomatic precursor conditions. SMM shows higher plasma cell counts than MGUS but still lacks organ damage. Both require careful monitoring, as they can progress to active MM 1 7 11.

Solitary Plasmacytoma

This rare variant involves a single site of disease, either within bone or soft tissue. There’s no widespread bone marrow involvement at diagnosis. Solitary plasmacytoma can evolve into classic MM 7 10.

Light Chain Myeloma and Other Variants

Some patients produce only light chains (Bence Jones proteins), which can be detected in urine and are associated with an increased risk of renal complications 10.

Genetic Subtypes

Genetic classification is increasingly important in MM. The main division is between hyperdiploid (extra odd-numbered chromosomes) and nonhyperdiploid (specific chromosomal translocations) myeloma. These genetic differences affect disease behavior and response to therapy 6 7 16.

Causes of Multiple Myeloma

While the exact cause of multiple myeloma remains unknown, research has identified several contributing factors—ranging from genetic mutations to environmental exposures and changes in the bone marrow environment.

Factor	Role/Description	Notable Details	Source(s)
Genetic mutations	Chromosomal translocations, trisomies	Initiate/progress MM	6 7 11
Microenvironment	Bone marrow milieu supports MM growth	Promotes progression	11 12
Radiation/toxins	Possible link to increased risk	Not fully established	13
Age	Incidence rises with age	Strongest risk factor	1 3
Immune dysfunction	Impaired immune surveillance	Allows MM persistence	9 12
Precursor states	MGUS/SMM can evolve into MM	Risk increases over time	1 7 11

Table 3: Causes and Risk Factors in Multiple Myeloma

Genetic Changes

Multiple myeloma begins with genetic mutations, especially chromosomal translocations involving the immunoglobulin heavy chain gene on chromosome 14. These mutations disrupt normal plasma cell growth and survival. Hyperdiploid MM features extra copies of chromosomes, while nonhyperdiploid MM involves specific translocations that activate cancer-driving genes 6 7 11.

The Bone Marrow Microenvironment

The bone marrow provides a nurturing environment for myeloma cells. Interactions between myeloma cells and surrounding stromal cells, immune cells, and soluble factors support tumor growth, protect against treatment, and suppress the immune response 11 12. This “soil” is as important as the “seed” (the cancer cell) in allowing MM to thrive.

Environmental and Lifestyle Factors

While there is no definitive environmental cause, some evidence suggests that radiation exposure and contact with certain industrial or agricultural chemicals may increase risk, though these links are not fully established 13.

Age and Precursor Conditions

Aging is the strongest risk factor—most patients are diagnosed in their 60s or older 1 3. MGUS and SMM are benign plasma cell disorders that can progress to MM over time, especially if certain genetic changes accumulate 1 7 11.

Immune System Dysfunction

Myeloma often develops in the context of a weakened immune system. MM cells evade immune detection and often actively suppress anti-tumor immune responses, contributing to both disease progression and infection risk 9 12.

Treatment of Multiple Myeloma

Treatment for multiple myeloma has evolved rapidly, offering new hope and longer survival for many patients. Therapy is highly individualized, considering patient age, disease stage, genetic risk, and overall health.

Treatment Modality	Description / Use	Key Drugs or Approaches	Source(s)
Chemotherapy	Kills malignant plasma cells	Melphalan, cyclophosphamide, etc.	1 7 16
Corticosteroids	Reduce inflammation, kill cells	Dexamethasone, prednisolone	1 16
Immunomodulatory drugs	Enhance immune attack	Thalidomide, lenalidomide, pomalidomide	1 7 18
Proteasome inhibitors	Block protein breakdown	Bortezomib, carfilzomib, ixazomib	1 14 17
Monoclonal antibodies	Target MM cell surface markers	Daratumumab, elotuzumab	15 18
Stem Cell Transplantation	Replace diseased marrow	Usually autologous (self)	1 7 16
Radiation therapy	Local bone disease/pain relief	Focal radiotherapy	1
Supportive Care	Manage complications/infection	Bisphosphonates, antibiotics, transfusions	1 4 9
Novel Therapies	Target new pathways/markers	CAR-T, bispecifics, BCMA-targeted	15 18

Table 4: Current Treatments for Multiple Myeloma

Standard Therapies

Chemotherapy and corticosteroids remain the backbone of initial therapy. These drugs are often combined to maximize effectiveness 1 7 16. Immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, boost the immune system’s ability to target cancer cells 1 7 18. Proteasome inhibitors like bortezomib disrupt the cancer cell’s ability to remove damaged proteins, triggering cell death 1 14 17.

Monoclonal Antibodies and Targeted Therapies

Newer drugs, such as daratumumab and elotuzumab, are monoclonal antibodies that specifically bind to proteins on myeloma cells, marking them for destruction by the immune system 15 18. These are often used in combination with other treatments.

Stem Cell Transplantation

For eligible patients, autologous stem cell transplantation (using the patient’s own cells) after high-dose chemotherapy can prolong survival and remission 1 7 16. However, not all patients are candidates due to age or other health factors.

Radiation and Supportive Care

Focal radiotherapy is used to treat isolated bone lesions or spinal cord compression 1. Supportive care is crucial and includes pain management (e.g., bisphosphonates, opiates), antibiotics for infection, and interventions for anemia or kidney problems 1 4 9.

Emerging and Future Therapies

CAR-T cell therapy, bispecific antibodies, and antibody-drug conjugates—particularly those targeting BCMA—represent the newest frontiers in treatment. These therapies can achieve deep responses in some patients, even those with refractory disease 15 18. Clinical trials remain essential for advancing care.

Personalized Treatment and Risk Stratification

Treatment plans are increasingly tailored based on genetic risk factors (e.g., high-risk cytogenetics) and patient-specific characteristics 16. New algorithms guide therapy selection, and ongoing research is aimed at overcoming drug resistance and minimizing side effects 16 17.

Conclusion

Multiple myeloma is a multifaceted disease that demands a nuanced understanding of its symptoms, types, causes, and treatments. The field is rapidly evolving, and while MM remains incurable for most, survival and quality of life are steadily improving thanks to advances in research and therapy.

Key Points:

• Symptoms: Bone pain, fatigue, anemia, kidney dysfunction, infections, and psychological distress are common and can severely impact quality of life 1 3 4 5.
• Types: Includes secretory, non-secretory, smoldering, MGUS, solitary plasmacytoma, and genetic subtypes, each with unique features and risks 1 6 7 8 10 11 16.
• Causes: Driven by genetic changes, bone marrow microenvironment, aging, and sometimes environmental exposures; precursor conditions like MGUS/SMM play a key role 6 7 11 12 13.
• Treatment: Involves a combination of chemotherapy, immunomodulators, proteasome inhibitors, monoclonal antibodies, stem cell transplantation, supportive care, and emerging immunotherapies 1 7 14 15 16 17 18.

Understanding these aspects empowers patients and families, enabling informed decision-making and more effective disease management. Ongoing research continues to bring new hope for even better treatments in the future.