While it may not dominate cancer headlines, multiple myeloma quietly accounts for nearly 1 in 10 of all blood cancers diagnosed in the United States, a disease marked by profound racial disparities where Black Americans face more than double the incidence of their White counterparts and diagnosed at a younger median age of 69 years.
Key Takeaways
- In 2023, an estimated 35,730 new cases of multiple myeloma were diagnosed in the United States, representing about 1.8% of all new cancer cases.
- The lifetime risk of developing multiple myeloma is approximately 0.8% for men and 0.6% for women in the US.
- Multiple myeloma accounts for 1.6% of all new cancer cases and 10.1% of all new hematologic malignancies in the US.
- Family history increases multiple myeloma risk by 2-4 fold.
- Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma at a rate of 1% per year.
- Obesity (BMI ≥30) is associated with a 1.8-fold increased risk of multiple myeloma.
- Bone pain, often in the back or ribs, is the most common initial symptom in 70% of multiple myeloma patients.
- Anemia occurs in 70% of patients at diagnosis, with hemoglobin <10 g/dL in 40%.
- Serum protein electrophoresis detects M-protein in 82% of newly diagnosed cases.
- Approximately 80% of newly diagnosed multiple myeloma patients receive bortezomib-based induction therapy.
- Autologous stem cell transplant (ASCT) improves progression-free survival by 12-18 months in transplant-eligible patients.
- Lenalidomide maintenance post-ASCT reduces risk of progression by 50%.
- The 5-year overall survival for multiple myeloma is 59.8% based on 2014-2020 data.
- Median overall survival for standard-risk myeloma is over 8 years with modern therapy.
- Patients with del(17p) have median PFS of 15 months vs 36 months without.
Multiple myeloma is a relatively rare blood cancer with significant disparities in risk and survival.
Diagnosis
- Bone pain, often in the back or ribs, is the most common initial symptom in 70% of multiple myeloma patients.
- Anemia occurs in 70% of patients at diagnosis, with hemoglobin <10 g/dL in 40%.
- Serum protein electrophoresis detects M-protein in 82% of newly diagnosed cases.
- CRAB criteria (hyperCalcemia, Renal failure, Anemia, Bone lesions) are present in 75% at diagnosis.
- Urine protein electrophoresis shows Bence Jones proteins in 75% of patients.
- Bone marrow plasma cells >60% confirm diagnosis in 95% of cases.
- Serum free light chain assay is abnormal in 97% of symptomatic myeloma patients.
- Skeletal survey reveals lytic lesions in 80% of patients at diagnosis.
- Hypercalcemia (>11 mg/dL) present in 25% at diagnosis.
- Renal insufficiency (creatinine >2 mg/dL) in 50% of newly diagnosed patients.
- Immunofixation identifies light chain type in 99% of M-protein cases.
- PET-CT detects bone disease in 90% sensitivity vs 70% for MRI.
- Fatigue is reported in 60-70% of patients prior to diagnosis.
- Beta-2 microglobulin >5.5 mg/L indicates high-risk disease in 70% of cases.
- Flow cytometry shows clonal plasma cells with CD38+, CD138+ in 95%.
- Whole-body low-dose CT has 92% sensitivity for lytic lesions.
- Recurrent infections due to hypogammaglobulinemia in 50% at diagnosis.
- LDH > upper normal limit prognosticates poor outcome in 40% high-risk cases.
- Cytogenetic abnormalities like del(17p) found in 10-15% at diagnosis via FISH.
- Plasmacytoma presents as solitary lesion in 3-5% of cases initially.
- SLiM criteria (Sixty% plasma cells, Light chain ratio >100, MRI lesions) for smoldering progression.
- Serum albumin <3.5 g/dL in 30% correlates with advanced disease.
- Weight loss >10% in 20% of patients at presentation.
- MRI detects focal lesions in 30% of smoldering myeloma cases.
- t(4;14) translocation in 15% of newly diagnosed patients.
- Neuropathy from amyloidosis in 5-10% of myeloma patients.
- ECOG performance status ≥2 in 40% at diagnosis.
- ISS stage III (beta2m >5.5, albumin <3.5) in 28% of patients.
Diagnosis Interpretation
Multiple myeloma is a statistical symphony of misery where your bones, blood, kidneys, and immune system form a grim quartet, with a 70% chance the overture is back pain and a 97% certainty the diagnostic tests will catch them in the act.
Epidemiology
- In 2023, an estimated 35,730 new cases of multiple myeloma were diagnosed in the United States, representing about 1.8% of all new cancer cases.
- The lifetime risk of developing multiple myeloma is approximately 0.8% for men and 0.6% for women in the US.
- Multiple myeloma accounts for 1.6% of all new cancer cases and 10.1% of all new hematologic malignancies in the US.
- The age-adjusted incidence rate of multiple myeloma in the US is 7.1 per 100,000 men and women per year based on 2017–2021 data.
- Incidence rates of multiple myeloma are more than twice as high in Black individuals (14.2 per 100,000) compared to White individuals (6.6 per 100,000).
- Globally, multiple myeloma represents 0.8% of all cancer diagnoses, with an estimated 160,039 new cases worldwide in 2020.
- The median age at diagnosis for multiple myeloma is 69 years, with only 2% of cases diagnosed under age 45.
- Men have a 1.5 times higher incidence rate of multiple myeloma than women (8.2 vs 5.6 per 100,000).
- From 2012–2021, the incidence rate of multiple myeloma increased by 1.5% annually on average in the US.
- Multiple myeloma is the second most common hematologic malignancy in the US after non-Hodgkin lymphoma.
- In Europe, the age-standardized incidence rate of multiple myeloma is 5.5 per 100,000 for men and 3.6 for women.
- Prevalence of multiple myeloma in the US is estimated at 142,422 individuals living with the disease as of 2023.
- Black Americans are diagnosed with multiple myeloma at nearly twice the rate of White Americans and at a younger age.
- In 2022, Australia reported 2,105 new cases of multiple myeloma, with an incidence rate of 8.1 per 100,000.
- The incidence of multiple myeloma has been rising by about 2% per year since the mid-1990s in the US.
- Multiple myeloma comprises 10-15% of all hematologic malignancies and 18% of plasma cell malignancies.
- In the UK, there are around 5,500 new multiple myeloma diagnoses annually, with a lifetime risk of 0.7%.
- Mortality from multiple myeloma decreased by 2.4% per year from 2013–2022 in the US.
- Multiple myeloma is responsible for 2.9% of all cancer deaths in the US.
- In Asia, multiple myeloma incidence is lower at 1-2 per 100,000 compared to 4-7 in Western countries.
- The 5-year relative survival rate for multiple myeloma improved from 47.6% (2004-2010) to 59.8% (2013-2019).
- Approximately 80% of multiple myeloma patients are over 60 years old at diagnosis.
- In Canada, multiple myeloma incidence is 6.3 per 100,000, with 3,000 new cases yearly.
- Hispanic Americans have an incidence rate of 6.9 per 100,000 for multiple myeloma.
- Multiple myeloma death rate is 20.9% higher in Black patients compared to White patients.
- Worldwide, multiple myeloma ranks as the 13th most common cancer in men and 17th in women.
- In the US, multiple myeloma is projected to have 35,000 new cases in 2024.
- Smoldering multiple myeloma prevalence is about 1 in 200 people over age 50.
- MGUS, a precursor to multiple myeloma, affects 3% of people over 50.
- Multiple myeloma incidence in Native Americans is 7.2 per 100,000.
Epidemiology Interpretation
While it remains a relatively rare cancer overall, multiple myeloma is a formidable and growing adversary, particularly for older adults and Black Americans, though recent advances are steadily turning the tide toward better survival.
Prognosis
- The 5-year overall survival for multiple myeloma is 59.8% based on 2014-2020 data.
- Median overall survival for standard-risk myeloma is over 8 years with modern therapy.
- Patients with del(17p) have median PFS of 15 months vs 36 months without.
- ISS stage I has 82% 5-year survival, stage III has 40%.
- High-risk cytogenetics (t(4;14), t(14;16), del(17p)) confer 2-3 fold worse prognosis.
- R-ISS stage III has median OS of 43 months.
- Transplant-eligible patients have 70% 5-year OS vs 50% ineligible.
- Median survival for relapsed/refractory myeloma is 9-12 months post-triple class exposure.
- MRD negativity (<10^-5) predicts >80% 3-year PFS.
- Renal failure at diagnosis halves median survival to 24 months.
- Gain(1q) abnormality worsens OS by 20-30 months.
- Elderly patients (>75 years) have 3-year OS of 50% vs 75% in <65.
- Triple-class refractory patients have median OS of 5.6 months.
- Black patients have 85% relative survival vs 92% for Whites, adjusted.
- Hypoalbuminemia (<3.5 g/dL) associated with 50% higher mortality risk.
- LDH >2x ULN predicts median OS of 18 months.
- Complete response rates correlate with >90% 5-year OS in standard risk.
- Extramedullary disease reduces median survival to 12-18 months.
- PCLI >5% indicates poor prognosis with median survival <2 years.
- 10-year OS for myeloma has improved to 37% from 25% a decade ago.
- Amyloidosis complicating myeloma halves survival to 12 months.
- High beta-2 microglobulin (>5.5 mg/L) stage III survival 50% at 3 years.
- Post-relapse survival averages 24 months with novel agents.
- t(11;14) has better prognosis than del(17p), median OS 60 vs 36 months.
- Performance status ECOG 0-1 predicts 70% 5-year OS.
- Plasma cell leukemia variant has median survival of 4-7 months.
- With quadruplet therapy, NDMM OS projected >10 years for 50%.
- Infection causes 20-25% of deaths in myeloma patients.
Prognosis Interpretation
While your prognosis in multiple myeloma feels like a cruel lottery, the drawn numbers are sadly predictable: your genetic profile, kidney function, and age are the sobering tickets that ultimately determine whether you're looking at a decade or a single year.
Risk Factors
- Family history increases multiple myeloma risk by 2-4 fold.
- Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma at a rate of 1% per year.
- Obesity (BMI ≥30) is associated with a 1.8-fold increased risk of multiple myeloma.
- African ancestry confers a 2-3 times higher risk of developing multiple myeloma compared to European ancestry.
- Exposure to radiation increases multiple myeloma risk by 2-5 fold in atomic bomb survivors.
- First-degree relatives of multiple myeloma patients have a 3.5-fold increased risk.
- Chronic antigenic stimulation from autoimmune diseases raises risk by 1.5-2 times.
- Pesticide exposure is linked to a 1.6-fold risk increase in farming populations.
- Smoking is associated with a 1.2-1.4 relative risk for multiple myeloma.
- High levels of monoclonal protein (>1.5 g/dL) in MGUS indicate 5-10% annual progression risk to myeloma.
- Abnormal free light chain ratio in MGUS predicts 2-3 fold higher progression risk.
- Male gender increases multiple myeloma risk by 1.2-1.5 times compared to females.
- Age over 65 doubles the risk compared to under 50.
- Working in agriculture or with solvents raises risk by 1.4 fold.
- Genetic mutations in 11q13 region increase risk by up to 4 times.
- Diabetes mellitus is associated with a 1.3-fold increased risk of multiple myeloma.
- Plasma cell dyscrasias like Waldenstrom macroglobulinemia share risk factors with 20% familial aggregation.
- Benign monoclonal gammopathy progresses to myeloma in 15-20% of cases over 10 years.
- High-risk smoldering myeloma has 50% progression risk within 2 years.
- African American men have the highest incidence, 2.4 times higher than White women.
- Ionizing radiation from medical imaging cumulatively increases risk by 1.1-1.5 fold.
- Hyperphosphorylation of proteins in myeloma cells linked to 30% higher familial risk.
- Alcohol consumption over 2 drinks/day reduces risk by 20-30% paradoxically.
- Physical inactivity increases risk by 1.2 fold in cohort studies.
- Hair dyes containing aromatic amines associated with 1.5-fold risk pre-1980.
Risk Factors Interpretation
While your family tree, expanding waistline, and even your morning hair dye ritual seem to be conspiring against you, remember that this rogue plasma cell party crasher is a complex negotiator influenced by genetics, luck, and lifestyle, not a single verdict.
Treatment
- Approximately 80% of newly diagnosed multiple myeloma patients receive bortezomib-based induction therapy.
- Autologous stem cell transplant (ASCT) improves progression-free survival by 12-18 months in transplant-eligible patients.
- Lenalidomide maintenance post-ASCT reduces risk of progression by 50%.
- Daratumumab added to VRd (D-VRd) achieves 88% very good partial response or better in NDMM.
- Median PFS with KRd (carfilzomib, lenalidomide, dex) is 34.2 months in NDMM.
- Bisphosphonates reduce skeletal-related events by 50% in myeloma patients.
- CAR-T therapy (idecabtagene vicleucel) shows 73% ORR in triple-class refractory myeloma.
- Pomalidomide plus dex achieves 31% ORR in refractory disease.
- Radiation therapy controls pain in 70-80% of painful bone lesions.
- Teclistamab (bispecific antibody) yields 63% ORR in heavily pretreated patients.
- Denosumab is non-inferior to zoledronic acid for SRE prevention, with 20% fewer renal toxicities.
- Quadruplet therapy GRIFFIN trial: D-VRd increases stringent CR by 42% vs 32%.
- Elotuzumab + Rd improves PFS to 19.4 months vs 14.9 months.
- Selinexor + dex achieves 25.3% ORR in penta-refractory myeloma.
- Tandem ASCT improves PFS by 10 months in high-risk patients.
- Venetoclax shows 40% response in t(11;14) positive relapsed myeloma.
- Isatuximab + Pd achieves 62.2% ORR in RRMM.
- Prophylactic antibiotics reduce infection risk by 30% during induction.
- Belantamab mafodotin ORR 32% in relapsed/refractory setting.
- VRd induction yields 80% response rate in transplant-eligible NDMM.
- Allogeneic transplant has 20-30% long-term remission but 15% TRM.
- Melphalan 200 mg/m2 conditioning for ASCT standard in 90% of cases.
- Talquetamab bispecific shows 70% ORR in RRMM.
- Rd maintenance post-ASCT: median PFS 52.8 months.
- Dialysis required in 20% of patients with renal failure, reversible in 50% with bortezomib.
- Cilta-cel CAR-T achieves 98% ORR and 83% MRD negativity.
Treatment Interpretation
We've built a remarkably layered artillery against multiple myeloma, starting with the foundational 80% of patients on bortezomib and ascending through precision strikes like 98% response CAR-T, all while diligently supporting the troops with bone protectors and infection shields.
Sources & References
- Reference 1CANCERcancer.orgVisit source
- Reference 2SEERseer.cancer.govVisit source
- Reference 3GCOgco.iarc.who.intVisit source
- Reference 4LLSlls.orgVisit source
- Reference 5ECISecis.jrc.ec.europa.euVisit source
- Reference 6MSKCCmskcc.orgVisit source
- Reference 7AIHWaihw.gov.auVisit source
- Reference 8NCBIncbi.nlm.nih.govVisit source
- Reference 9CANCERRESEARCHUKcancerresearchuk.orgVisit source
- Reference 10PUBMEDpubmed.ncbi.nlm.nih.govVisit source
- Reference 11MYELOMAmyeloma.org.ukVisit source
- Reference 12CANCERcancer.caVisit source
- Reference 13MAYOCLINICmayoclinic.orgVisit source
- Reference 14CANCERcancer.govVisit source
- Reference 15HEMATOLOGYhematology.orgVisit source
- Reference 16NEJMnejm.orgVisit source
- Reference 17THELANCETthelancet.comVisit source