Multiple MyelomaMultiple Myeloma

Morning ReportMorning ReportJuly 21, 2009July 21, 2009

Lindsay KruskaLindsay Kruska

Multiple MyelomaMultiple Myeloma Neoplastic proliferation of single clone of Neoplastic proliferation of single clone of

plasma cells producing monclonal plasma cells producing monclonal immunoglobulinimmunoglobulin

Cause unknownCause unknown Radiation and solvents ?associatedRadiation and solvents ?associated

1% malignancy, 10% hematologic 1% malignancy, 10% hematologic malignancy in USmalignancy in US Incidence 4-5/100,000Incidence 4-5/100,000

Median age presentation 60-66y, rare <40y Median age presentation 60-66y, rare <40y (2%)(2%)

Presentation: SymptomsPresentation: Symptoms Suspected usually due to widely varied Suspected usually due to widely varied

symptoms (>6mo in 40%)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 compressionSx of cord compression Repeated infections (pneumonia, pyelonephritis)Repeated infections (pneumonia, pyelonephritis)

Presentation: SignsPresentation: Signs Physical ExamPhysical Exam

PallorPallor Organomegaly, palpable LN rare (<5%)Organomegaly, palpable LN rare (<5%) Radiculopathy (cord compression) (5%)Radiculopathy (cord compression) (5%) Peripheral neuropathy uncommonPeripheral neuropathy uncommon

LabsLabs Hypercalcemia (36%)Hypercalcemia (36%) Increased serum total proteinIncreased serum total protein Anemia (34%)Anemia (34%) Acute renal failure (34%)Acute renal failure (34%) Low anion gapLow anion gap

Work upWork up CBC with diff, smearCBC with diff, smear

Anemia, rouleauxAnemia, rouleaux ChemistriesChemistries

Ca, Creatinine, Total proteinCa, 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 chainsSerum light chains Beta-2 microglobulinBeta-2 microglobulin Bone marrow biopsyBone marrow biopsy Bone survey, occasionally advanced imagingBone survey, occasionally advanced imaging

SPEPSPEP

Electrophoresis Immunofixation

Bone Marrow BiopsyBone Marrow Biopsy Marrow Marrow

plasmacytosis plasmacytosis (>10%)(>10%) CD138+, CD138+,

monoclonalmonoclonal Focal BM Focal BM

involvementinvolvement 10% require 10% require

multiple biopsiesmultiple biopsies

Bony involvementBony involvement

DiagnosisDiagnosis Presence of serum and/or urine Presence of serum and/or urine

monoclonal proteinmonoclonal 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 plasmacytomaClonal plasma cells or plasmacytoma End organ damageEnd organ damage

HyperHyperCCa, a, RRenal failure, enal failure, AAnemia, Lytic nemia, Lytic BBone lesionsone lesions

Main Differential Diagosis: Main Differential Diagosis: Elevated M proteinElevated M protein

MGUS (1%/year)MGUS (1%/year) Absence of symptomsAbsence 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 lesionsNo 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 amyloidosisPrimary amyloidosis Metastatic cancerMetastatic cancer

Differential Also IncludesDifferential Also Includes Other lymphoid Other lymphoid

neoplasms neoplasms CLLCLL B and T cell lymphomasB and T cell lymphomas

Non lymphoid Non lymphoid neoplasmsneoplasms Breast CaBreast Ca CMLCML Breast and colon cancerBreast and colon cancer

CirrhosisCirrhosis SarcoidosisSarcoidosis

Gaucher’s diseaseGaucher’s disease Pyoderma Pyoderma

gangrenosumgangrenosum Autoimmune Autoimmune

conditionsconditions Myasthenia gravisMyasthenia gravis Rheumatoid arthritisRheumatoid arthritis Cold agglutinin diseaseCold agglutinin disease

Several rare skin DOSeveral rare skin DO

StagingStaging Durie-Salmon staging (Stages I-III, a/b), Durie-Salmon staging (Stages I-III, a/b),

19751975 M protein M protein Serum Calcium Serum Calcium Radiographic Bone InvolvementRadiographic Bone Involvement HemoglobinHemoglobin Renal failureRenal failure

International Staging System (Stages I-III), International Staging System (Stages I-III), 20052005 Serum beta2 microglobulinSerum beta2 microglobulin AlbuminAlbumin

TherapyTherapy Supportive careSupportive care

Hypercalcemia/bone involvement: usual therapies, Hypercalcemia/bone involvement: usual therapies, analgesia, occ XRTanalgesia, occ XRT

Renal involvement: adequate hydration, ?plasmapheresisRenal involvement: adequate hydration, ?plasmapheresis Low threshold for infectious complications Low threshold for infectious complications Hyperviscosity: plasmapheresisHyperviscosity: plasmapheresis Neurologic compromise: palliative radiationNeurologic compromise: palliative radiation Anemia: transfusionAnemia: transfusion

Initation of specific therapyInitation of specific therapy ChemotherapyChemotherapy

ThalidomideThalidomide DexamethasoneDexamethasone Melphalan/prednisoneMelphalan/prednisone Bortezomib (proteasome inhibitor)Bortezomib (proteasome inhibitor)

HSCTHSCT

PrognosisPrognosis Usually fatalUsually fatal

10-20% mortality within first 2 months10-20% mortality within first 2 months Mean survival 4-5yMean survival 4-5y

5y survival 31%, 10y 10%, 15y 4%5y survival 31%, 10y 10%, 15y 4% Delay in diagnosis associated with negative impact Delay in diagnosis associated with negative impact

on disease courseon disease course Lead time biasLead time bias

Improved survival with therapy including HSCTImproved survival with therapy including HSCT Major causes of death: progressive myeloma, renal Major causes of death: progressive myeloma, renal

failure, sepsis, therapy related acute leukemia or failure, sepsis, therapy related acute leukemia or myelodisplasia; 25% die of age related illnessesmyelodisplasia; 25% die of age related illnesses

ReferencesReferences Fauci, et al. Harrison’s Internal Fauci, et al. Harrison’s Internal

Medicine. 17Medicine. 17thth edition. edition. Abeloff, et al. Abeloff's Clinical Abeloff, et al. Abeloff's Clinical

Oncology, 4th ed. Oncology, 4th ed. Up to Date. www.utdol.com Up to Date. www.utdol.com