Multiple Myeloma

Morning Report
July 21, 2009
Lindsay Kruska
 Multiple Myeloma
 Neoplastic proliferation of single clone of plasma
cells producing monclonal immunoglobulin
 Cause unknown
 Radiation and solvents ?associated
 1% malignancy, 10% hematologic malignancy in
US
 Incidence 4-5/100,000
 Median age presentation 60-66y, rare <40y
(2%)
 Presentation: Symptoms
 Suspected usually due to widely varied
symptoms (>6mo in 40%)
 Bone pain (67%)
 Weakness and Fatigue (30%)
 Weight loss (24%)
 Asthenia (14%)
 Dyspnea (4%)
 Fever (<1%)
 Sx of cord compression
 Repeated infections (pneumonia, pyelonephritis)
 Presentation: Signs
 Physical Exam
 Pallor
 Organomegaly, palpable LN rare (<5%)
 Radiculopathy (cord compression) (5%)
 Peripheral neuropathy uncommon
 Labs
 Hypercalcemia (36%)
 Increased serum total protein
 Anemia (34%)
 Acute renal failure (34%)
 Low anion gap
Work up
 CBC with diff, smear
 Anemia, rouleaux
 Chemistries
 Ca, Creatinine, Total protein
 SPEP with immunofixation (87% sensitive)
 UPEP (24h urine) (75% sensitive)
 Serum light chains
 Beta-2 microglobulin
 Bone marrow biopsy
 Bone survey, occasionally advanced imaging
 SPEP

Electrophoresis Immunofixation
 Bone Marrow Biopsy
 Marrow plasmacytosis
(>10%)
 CD138+, monoclonal
 Focal BM involvement
 10% require multiple
biopsies
Bony involvement
 Diagnosis
 Presence of serum and/or urine
monoclonal protein
 IgG (53%), IgA (25%), IgD (1%)
 Free light chains (20%)
 Clonal plasma cells or plasmacytoma
 End organ damage
 HyperCa, Renal failure, Anemia, Lytic Bone
lesions
Main Differential Diagosis: Elevated
M protein
 MGUS (1%/year)
 Absence of symptoms
 M protein <3g/L
 <10% plasma cells in marrow
 No anemia, renal failure, hyperCa, lytic lesions
 Smoldering Multiple Myeloma (10%/year)
 Meets dx criteria for MM but no end organ
 Primary amyloidosis
 Metastatic cancer
 Differential Also Includes
 Other lymphoid  Gaucher’s disease
neoplasms  Pyoderma gangrenosum
CLL

 Autoimmune conditions
 B and T cell lymphomas
 Myasthenia gravis
 Non lymphoid neoplasms  Rheumatoid arthritis
 Breast Ca  Cold agglutinin disease
CML

 Several rare skin DO
 Breast and colon cancer
 Cirrhosis
 Sarcoidosis
 Staging
 Durie-Salmon staging (Stages I-III, a/b), 1975
 M protein
 Serum Calcium
 Radiographic Bone Involvement
 Hemoglobin
 Renal failure
 International Staging System (Stages I-III),
2005
 Serum beta2 microglobulin
 Albumin
 Therapy
 Supportive care
 Hypercalcemia/bone involvement: usual therapies, analgesia,
occ XRT
 Renal involvement: adequate hydration, ?plasmapheresis
 Low threshold for infectious complications
 Hyperviscosity: plasmapheresis
 Neurologic compromise: palliative radiation
 Anemia: transfusion
 Initation of specific therapy
 Chemotherapy
 Thalidomide
 Dexamethasone
 Melphalan/prednisone
 Bortezomib (proteasome inhibitor)
 HSCT
 Prognosis
 Usually fatal
 10-20% mortality within first 2 months
 Mean survival 4-5y
 5y survival 31%, 10y 10%, 15y 4%
 Delay in diagnosis associated with negative impact on
disease course
 Lead time bias
 Improved survival with therapy including HSCT
 Major causes of death: progressive myeloma, renal
failure, sepsis, therapy related acute leukemia or
myelodisplasia; 25% die of age related illnesses
 References

 Fauci, et al. Harrison’s Internal Medicine.

17th edition.
 Abeloff, et al. Abeloff's Clinical Oncology,
4th ed.
 Up to Date. www.utdol.com