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Miten R. Patel, MD Cancer Specialists of North Florida

Plasma Cell Dyscrasias. Miten R. Patel, MD Cancer Specialists of North Florida. Disclosures. None. Objectives. Review types of Plasma cell dyscrasias Epidemiology and definitions Presenting signs and symptoms Myeloma staging Couple of cases Treatment overview. Plasma Cell Dyscrasias.

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Miten R. Patel, MD Cancer Specialists of North Florida

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  1. Plasma Cell Dyscrasias Miten R. Patel, MD Cancer Specialists of North Florida

  2. Disclosures • None

  3. Objectives • Review types of Plasma cell dyscrasias • Epidemiology and definitions • Presenting signs and symptoms • Myeloma staging • Couple of cases • Treatment overview

  4. Plasma Cell Dyscrasias • Monoclonal Gammopathy of Unknown Significance (MGUS) • Smoldering Myeloma (SMM) • Multiple Myeloma (MM) • Waldenstroms Macroglobulinemia (WM) • Amyloidosis • Solitary plasmacytoma • POEMS syndrome

  5. MGUS • Mean age at diagnosis – 70yo • M>F, incidence increases with age, found in 1-2% of adults • African Americans 2-3x > Caucasians • Present in 3% of persons >50 and 5% of persons over the age of 70 • Most cases sporadic but relatives of patients with MGUS/myeloma have an increased risk (RR 2-3)

  6. MGUS • Definition • Serum monoclonal protein <3g/dL, bone marrow plasma cells <10%, and absence of end organ damage • Hypercalcemia • Renal Failure • Anemia/Thrombocytopenia • Lytic bone lesions

  7. MGUS • Non-IgM MGUS • Progresses to myeloma • Rarely, to AL amyloid, light chain disease or other lymphoproliferative disorder • IgM MGUS • Progresses to Waldenstroms macroglobulinemia • Rarely, to myeloma, AL amyloidosis or lymphoma

  8. MGUS • Part of the spectrum of smoldering myeloma and multiple myeloma • Characterized by a monoclonal protein level of <30 g/L (m spike of 3.0 g/dL), <10% plasma cells in the bone marrow • Progression to MM or related disorder is about 1% per year. • Clinically asymptomatic premalignant condition

  9. MGUS • No symptoms? • Pts. identified when undergoing testing for other conditions such as neuropathy, vasculitis, hemolytic anemia, rashes, hypercalcemia, elevated ESR, elevated total protein • Likely had existed for years before diagnosis • Finding on labs - usually elevated total protein, immunoglobulin, abnormal SPEP/UPEP, positive IFE, or abnormal light chain ratio

  10. MGUS – Workup • Labs - CBC + diff, BMP (Cr, Ca), SPEP + IFE, Quant Igs, 24 urine IFE, B2 microglobulin, albumin, serum free light chains • Imaging – Skeletal survey, Certain cases - MRI & PET scan • Bone Marrow biopsy & aspirate • Cytogenetics & FISH studies

  11. MGUS • Once confirmed (Monoclonal protein <3 g/dL, <10% plasma cells, no CRAB symptoms) – no treatment • Serial followup, every 3-6 months, exam, assessment and labs, less often after 2 years. • Monitor for developing symptoms (bone pain, hypercalcemia, kidney dysfunction, anemia, etc) • SMM – every 3 months until progression • No treatment unless symptomatic MM

  12. Smoldering Myeloma • Smoldering Myeloma (aka asymptomatic multiple myeloma) • Same as MM but without symptoms and • Hgb > 10.5, • Monoclonal Ig Peak (usually > 3g/dL and/or >10 but <60% clonal plasma cells) • Normal serum Ca and Cr levels • No lytic bone lesions • REQUIRES NO TREATMENT • >60% plasma cells or FLC ratio >100 even without end organ damage, best classified as multiple myeloma

  13. Multiple Myeloma • Presentation • Weakness, Fatigue, Pallor (32%) • Weight Loss (24%) • Radiculopathy, cord compression • Bone pain (58%), fractures • Recurrent infections (dysfunctional immunoglobulin) • Labs – Anemia (73%), hypercalcemia (28%), elevated total protein, kidney dysfunction (48%)

  14. Multiple Myeloma • Rouleaux Formation • Elevated Sed Rate • Elevated C Reactive Protein • Normocytic, normochromic anemia • Renal Disease, Cr > 2mg/dL in 19% • Renal insufficiency caused by cast nephropathy (myeloma kidney) or hypercalcemia • Altered mental status caused by hypercalcemia and hyperviscosity

  15. Multiple Myeloma • Monoclonal Ig • IgG 60% • IgA 20% • Light chain only 18% (K>L) • IgM, IgD, IgE, non-secretory < 1% • For nonsecretory myeloma (no M protein) or light chain only, diagnosis is often made with bony lesions and plasmacytosis by bone marrow

  16. MyelomaBone Marrow Aspirate

  17. MyelomaBlood Smear

  18. Myeloma StagingDurie Salmon • Stage 1 • Ca <12, Hgb >10, Normal skeletal survey or solitary plasmacytoma, low M protein with IgG <5 g/dL or IgA <3 g/dL, Bence Jones protein <4g/24h • Stage 2 • Neither stage 1 or 3 • Stage 3 • One of the following: Hgb <8.5, Ca >12, multiple lytic lesions, high M component (IgG >7, IgA >5 or Bence Jones >12gm)

  19. Myeloma StagingISS • Stage 1 • B2M ≤3.5 and albumin ≥3.5 • Stage 2 • B2M >3.5 but <5.5 or albumin >3.5 • Stage 3 • B2M ≥5.5

  20. Case Presentation • 41yo WF with no symptoms goes to annual physical at office based clinic. • No symptoms other than mild fatigue • Routine annual labs drawn

  21. Lab draw #1

  22. Lab draw #2

  23. Lab draw #3

  24. Lab draw #4

  25. Bone Marrow Biopsy

  26. Myeloma Treatment • Determine eligibility for HDT and SCT • Age, overall health, psychological evaluation • Avoid alkylating agents (marrow toxic) • Chemotherapy to induce remission • Refer for stem cell collection and transplant • Maintenance therapy • Regular monitoring • ASCT improves median OS by >12 months

  27. Myeloma Treatment • Transplant ineligible • Immunomodulators (Thalidomide, Revlimid, Pomalyst) • DVT risk • Proteosome inhibitors (Velcade, Kyprolis) • Chemotherapy (MP, VAD, Doxil, HyperCVAD) • Supportive care • Bisphosphonates

  28. Myeloma Treatment

  29. Solitary Plasmacytoma • Approx 3% of myeloma patients • No or very low myeloma protein in serum or urine • MR must be done to evaluate patient as it may detect other bone lesions (upstage the patient to myeloma) • Presence of monoclonal protein >1yr after irradiation denotes progression to myeloma • Treat with XRT (at least 45 Gy). • MM manifests overtime, only 20% remain disease free at 10 yrs • Median time to progression is 2 yrs

  30. Waldenstrom’s • Lymphoplasmacytic bone marrow infiltration • Malignant B lymphocytes producing monoclonal IgM • Median age 65; Whites > Blacks; M>F • 1500 cases in the US per year • Hyperviscosity syndromes • neurologic complaints including vision change, headache, vertigo, nystagmus, dizziness, deafness, diplopia and ataxia • 10-20% of pts. Have a cryoglobulin (Type I) which precipitates at high T >22C on cold exposure may cause symptoms such as Raynauds phenomenon, urticaria, purpura and acral cyanosis. • Diarrhea and Steatorrhea (IgM infiltration into GI tract)

  31. Waldenstrom’s

  32. Waldenstrom’s Treatment • Goal to reduce hyperviscosity (IgM is a pentamer!) and lymphoproliferation • Pheresis if symptoms from the hyperviscosity causing severe neurologic deficits • Chemotherapy • Chlorambucil, other CCU, Cladribine and Fludarabine, Rituxan, IFN, Thalidomide, Ibrutinib, Velcade

  33. Case #2 • 73yo WF presenting with neuropathy, dizziness, 40lb weight loss, IgM 5454, immediately hospitalized due to neurologic symptoms, started plasma exchange

  34. Case #2 • Bone Marrow • Bone marrow, flow cytometric immunophenotypic analysis: Monoclonal plasma cells and lymphocytes identified, consistent with Waldenstrom's macroglobulinemia.

  35. Case #2 • Dramatic decline in IgM (>5000 to <2000) after plasma exchange • Symptoms have improved • Treated with Rituxan and Velcade, IgM started rising again. • Changed to Ibrutinib, symptoms remain improved, IgM stabilized below 1500 • IgM stable for > 2 years now

  36. Amyloidosis • Occurs in 10% of patients with MM • Infiltrative process resulting from amyloid fibril deposition in organs • Fibril is made from the terminal amino acid residue (NH2) of the variable portion of the light chain Ig molecule • Produced by clonal plasma cells

  37. Amyloidosis • Renal disease - asymptomatic proteinuria to nephrotic syndrome • Cardiomyopathy • Hepatomegaly • Neuropathy • Pseudohypertrophy of muscles • Bleeding problems (Factor X def, Liver dz) • Lung and Skin infiltration

  38. Amyloidosis

  39. Amyloidosis • AL should be suspected in patients with plasma cell dyscrasia history • Biopsy results as shown • SPEP/UPEP - confirms monoclonal protein (plasma cell population) • Treatment - treat underlying plasma cell dyscrasia

  40. Summary • MGUS, SMM and MM are a spectrum of the same disease process • MGUS and SMM patients need close observation • WM patients present with hyperviscosity symptoms and very high IgM, total protein • Amyloidosis (AL) is characterized by fibril deposition in organs with damage (most commonly heart/liver/kidney) • Treatment is dependant on the disease process

  41. Questions Miten R. Patel, MD Office 904-516-3737 Cell phone 904-451-9820 miten.patel@csnf.us

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