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Multiple Myeloma

Multiple Myeloma. Andrew H. Baker PGY-2 Emory Family Medicine 02/18/2010. Epidemiology. Elderly (mean age 68 years).  How common 5/100,000 Prevalence = 50,000 persons in United States Incidence= 16,000 cases/year in United States Twice as common in black persons Men > Women 

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Multiple Myeloma

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  1. Multiple Myeloma Andrew H. Baker PGY-2 Emory Family Medicine 02/18/2010

  2. Epidemiology • Elderly (mean age 68 years).  • How common • 5/100,000 • Prevalence = 50,000 persons in United States • Incidence= 16,000 cases/year in United States • Twice as common in black persons • Men > Women  • Family History = 4 fold increased risk (autosomal dominant) • Associated conditions: Obesity, RA, MGUS • Occupational Exposures: • Ionizing radiation • Farming pesticides,  • Petroleum Workers.

  3. Epidemiology • MGUS • Premalignant condition • Abnormal production of monoclonal Ig by plasma cell • This also happens in MM, however: • Fewer M-proteins • No End Organ Damage • 2 percent population > 50 years • Risk of progressing to MM > 1 percent each year.

  4. Pathophysiology • Normally, plasma cells produce immunoglobulins to fight infection  • However, in MM and MGUS a single cloned plasma cell proliferate and overproduce the same Ig (aka, the "M-protein" or "paraprotein." ) • The M-protein is usually an IgG • MM cells can also just produce the light chain component (Instead of the entire Ig)

  5. Pathophysiology • Consequence of producing lots of monoclonal Ig:  • Hyperviscosity • Kidney Damage (from light chains only) • Bone pain, hypercalcemia and pathologic fractures from bone lesions. • Anemia/Pancytopenia from bone marrow invasion

  6. Pathophysiology • 80% of cases of MM arise De Novo • 20% percent from MGUS. • Risk factors for progression from MGUS to MM include: • An elevated M protein level > 1.5 g per dL • A non-IgG MGUS • Abnormal free light chain ratio  • Patients with MGUS should be monitored closely q 6 to 12 months. (C-Level)

  7. Clinical Presentation • Many patients (58%) initially present with unexplained backache or bone pain.   • The long bones, ribs, skull, and pelvis are also commonly involved, and most patients have multiple lytic skeletal lesions.  • Pathologic fracture is the presenting symptom in 26 to 34 %  • Anemia (73%), Elevated BUN (48%), Fatigue/weakness(33%), Hypercalcemia (28%), Weight loss (25%)  • Other: Recurrent infections, Headaches/visual changes, parenthesizes (5%), fever, organomegaly (1%).

  8. Clinical Presentation • 34 percent of patients are asymptomatic at presentation with incidental findings • Increased Total protein,  • Renal Inefficiency, Cr > 2 • Hypercalcemia > 11 • Anemia, Hemoglobin < 10 • More asymptomatic patients being identified with increase in "routine blood work."

  9. Rare presentations • Soft tissue or solitary bone masses (plasmacytomas) • Hyperviscosity-induced arterial infarctions or venous thrombosis • Concomitant amyloidosis with gastrointestinal symptoms, peripheral neuropathy, or cardiomegaly

  10. Helpful Mnemonic • C - calcium • R - renal • A - anemia • B - bone

  11. Diagnosis - Tests • SPEP & UPEP w/ immunofixation (C - level) • 80% patients w/ + SPEP • The remainder have + UPEP  only • About 3% have "non secretory" MM ( Neg SPEP & UPEP) • Urine dipstick tests • Classic Test for Bence Jones Proteins, but insensitive • Bone marrow • Anyone with abnormal SPEP/UPEP • May required multiple aspirates for focal dyscrasias • CBC, peripheral smear, BUN/CR, Ca, ESR

  12. Imaging Work up • Skeletal Survey • Skull, spine, long bones, ribs, pelvis • MRI • More sensitive • But, generally reserved for suspected spinal lesions

  13.  Presenting Diagnostic Abnormalities in MM Abnormality                                                             Percentage SPEP or UPEP+                                                              97 SPEP_+                                                                            82 SPEP w/Immunofixation                                             93 UPEP+                                                                             75 > 10% bone marrow plasma cells                                90 Bone lesions on radiography                                        75 Hemoglobin level of < 12 g                                           65 Creatinine  > 2 mg per dL                                             23 Calcium >  11 mg per                                                      13

  14. Diagnosis • Asymptomatic "smoldering" multiple myeloma • Serum M protein level of > 3 g per dL   • > 10 % plasma cells on bone marrow • CRAB neg • Symptomatic multiple myeloma  • M protein (any level) • Presence of clonal plasma cells (any level) • CRAB Positive

  15. DDx • Waldenstrom's • Solitary plasmacytoma • Primary amylodoisis • POEM • Metastatic Ca

  16. Treatment - Asymptomatic MM • Observation only with labs q 3 to 4 months • Early treatment may worsen prognosis (Level A) • Prognosis based on % plasma cells and M-protein level

  17. Treatment - Symptomatic Disease • Autologous stem cell transplantation (ASCT) is treatment of choice • Older patients > 65 may not physically tolerate procedure • ASCT proceeded by chemotherapy induction protocols (vincristine,  doxorubicin, dexamethasone, thalidomide) • FP should be aware of the adverse effects of thalidomide • e.g., somnolence, neuropathy, deep venous thrombosis • Thalidomide neuropathy may not be resersible. • 5 year survival 35%

  18. Managing compliations of MM • Osteoporosis/bone pain/fractures • All patients should be on bisphosphonate (A level) • IV  pamidronate and zoledronic acid used most commonly, q 4 weeks dosing • Orthopedic referral ==> Radiotherapy, vertebroplasty/kyphoplasty • Hypercalcemia • Aggressive hydration, corticosteroids, lasix PRN bisphosphonates

  19. Managing compliations of MM • Renal Insufficiency • Identifying reversible causes. Dialysis PRN.  • Plasmaphereis for hyperviscosity induced thrombosis • Anemia • Erythopoetin, Transfusion • Infection • Treat aggressively with broad spectrum antibiotics •  Vaccinations (B level) • FLU, PNA, HIB

  20. Summary • Consider MM in elderly patients with new onset bone pain/fatigue/CRAB symptoms not resolving with treatment • Basic work up: SPEP/UPEP (+/- immunofixation), CBC, peripheral smear, BUN/CR, Ca, skeletal survey • DDx, MGUS, asymptomatic vs symptomatic, Waldenstrom’s, Amyloidosis, NHL, etc.. • No Tx for MGUS and asymptomatic MM. • Manage Complications: Bisphosphonates, orthopedics referral PRN, Vaccination, CRAB.

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