Multiple Myeloma Morning Report July 21, 2009 Lindsay Kruska

Multiple Myeloma Neoplastic proliferation of single clone of plasma cells producing monclonal immunoglobulin Neoplastic proliferation of single clone of plasma cells producing monclonal immunoglobulin Cause unknown Cause unknown Radiation and solvents ?associated Radiation and solvents ?associated 1% malignancy, 10% hematologic malignancy in US 1% malignancy, 10% hematologic malignancy in US Incidence 4-5/100,000 Incidence 4-5/100,000 Median age presentation 60-66y, rare <40y (2%) Median age presentation 60-66y, rare <40y (2%)

Presentation: Symptoms Suspected usually due to widely varied symptoms (>6mo in 40%) Suspected usually due to widely varied symptoms (>6mo in 40%) Bone pain (67%) Bone pain (67%) Weakness and Fatigue (30%) Weakness and Fatigue (30%) Weight loss (24%) Weight loss (24%) Asthenia (14%) Asthenia (14%) Dyspnea (4%) Dyspnea (4%) Fever (<1%) Fever (<1%) Sx of cord compression Sx of cord compression Repeated infections (pneumonia, pyelonephritis) Repeated infections (pneumonia, pyelonephritis)

Presentation: Signs Physical Exam Physical Exam Pallor Pallor Organomegaly, palpable LN rare (<5%) Organomegaly, palpable LN rare (<5%) Radiculopathy (cord compression) (5%) Radiculopathy (cord compression) (5%) Peripheral neuropathy uncommon Peripheral neuropathy uncommon Labs Labs Hypercalcemia (36%) Hypercalcemia (36%) Increased serum total protein Increased serum total protein Anemia (34%) Anemia (34%) Acute renal failure (34%) Acute renal failure (34%) Low anion gap Low anion gap

Work up CBC with diff, smear CBC with diff, smear Anemia, rouleaux Anemia, rouleaux Chemistries Chemistries Ca, Creatinine, Total protein Ca, Creatinine, Total protein SPEP with immunofixation (87% sensitive) SPEP with immunofixation (87% sensitive) UPEP (24h urine) (75% sensitive) UPEP (24h urine) (75% sensitive) Serum light chains Serum light chains Beta-2 microglobulin Beta-2 microglobulin Bone marrow biopsy Bone marrow biopsy Bone survey, occasionally advanced imaging Bone survey, occasionally advanced imaging

SPEP ElectrophoresisImmunofixation

Bone Marrow Biopsy Marrow plasmacytosis (>10%) Marrow plasmacytosis (>10%) CD138+, monoclonal CD138+, monoclonal Focal BM involvement Focal BM involvement 10% require multiple biopsies 10% require multiple biopsies

Bony involvement

Diagnosis Presence of serum and/or urine monoclonal protein Presence of serum and/or urine monoclonal protein IgG (53%), IgA (25%), IgD (1%) IgG (53%), IgA (25%), IgD (1%) Free light chains (20%) Free light chains (20%) Clonal plasma cells or plasmacytoma Clonal plasma cells or plasmacytoma End organ damage End organ damage HyperCa, Renal failure, Anemia, Lytic Bone lesions HyperCa, Renal failure, Anemia, Lytic Bone lesions

Main Differential Diagosis: Elevated M protein MGUS (1%/year) MGUS (1%/year) Absence of symptoms Absence of symptoms M protein <3g/L M protein <3g/L <10% plasma cells in marrow <10% plasma cells in marrow No anemia, renal failure, hyperCa, lytic lesions No anemia, renal failure, hyperCa, lytic lesions Smoldering Multiple Myeloma (10%/year) Smoldering Multiple Myeloma (10%/year) Meets dx criteria for MM but no end organ Meets dx criteria for MM but no end organ Primary amyloidosis Primary amyloidosis Metastatic cancer Metastatic cancer

Differential Also Includes Other lymphoid neoplasms Other lymphoid neoplasms CLL CLL B and T cell lymphomas B and T cell lymphomas Non lymphoid neoplasms Non lymphoid neoplasms Breast Ca Breast Ca CML CML Breast and colon cancer Breast and colon cancer Cirrhosis Cirrhosis Sarcoidosis Sarcoidosis Gaucher’s disease Gaucher’s disease Pyoderma gangrenosum Pyoderma gangrenosum Autoimmune conditions Autoimmune conditions Myasthenia gravis Rheumatoid arthritis Cold agglutinin disease Several rare skin DO Several rare skin DO

Staging Durie-Salmon staging (Stages I-III, a/b), 1975 Durie-Salmon staging (Stages I-III, a/b), 1975 M protein M protein Serum Calcium Serum Calcium Radiographic Bone Involvement Radiographic Bone Involvement Hemoglobin Hemoglobin Renal failure Renal failure International Staging System (Stages I-III), 2005 International Staging System (Stages I-III), 2005 Serum beta2 microglobulin Serum beta2 microglobulin Albumin Albumin

Therapy Supportive care Supportive care Hypercalcemia/bone involvement: usual therapies, analgesia, occ XRT Hypercalcemia/bone involvement: usual therapies, analgesia, occ XRT Renal involvement: adequate hydration, ?plasmapheresis Renal involvement: adequate hydration, ?plasmapheresis Low threshold for infectious complications Low threshold for infectious complications Hyperviscosity: plasmapheresis Hyperviscosity: plasmapheresis Neurologic compromise: palliative radiation Neurologic compromise: palliative radiation Anemia: transfusion Anemia: transfusion Initation of specific therapy Initation of specific therapy Chemotherapy Chemotherapy Thalidomide Thalidomide Dexamethasone Dexamethasone Melphalan/prednisone Melphalan/prednisone Bortezomib (proteasome inhibitor) Bortezomib (proteasome inhibitor) HSCT HSCT

Prognosis Usually fatal Usually fatal 10-20% mortality within first 2 months 10-20% mortality within first 2 months Mean survival 4-5y Mean survival 4-5y 5y survival 31%, 10y 10%, 15y 4% 5y survival 31%, 10y 10%, 15y 4% Delay in diagnosis associated with negative impact on disease course Delay in diagnosis associated with negative impact on disease course Lead time bias Lead time bias Improved survival with therapy including HSCT 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 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. 17 th edition. Fauci, et al. Harrison’s Internal Medicine. 17 th edition. Abeloff, et al. Abeloff's Clinical Oncology, 4th ed. Abeloff, et al. Abeloff's Clinical Oncology, 4th ed. Up to Date. Up to Date.