Download Plasma Cell Dyserasias

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
• Monoclonal Gammopathy of Unknown Significance
(MGUS)
• Smoldering Myeloma (SMM)
• Multiple Myeloma (MM)
• Waldenstroms Macroglobulinemia (WM)
• Amyloidosis
• Solitary plasmacytoma
• POEMS syndrome
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)
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
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
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
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
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
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
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
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%)
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
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
Myeloma
Bone Marrow Aspirate
Myeloma
Blood Smear
Myeloma Staging
Durie 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)
• Stage 1
Myeloma Staging
ISS
– B2M ≤3.5 and albumin ≥3.5
• Stage 2
– B2M > 3.5 but <5.5 or albumin >3.5
• Stage 3
– B2M ≥5.5
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
Lab draw #1
Lab draw #2
Lab draw #3
Lab draw #4
Bone Marrow Biopsy
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
Myeloma Treatment
• Transplant ineligible
– Immunomodulators (Thalidomide, Revlimid,
Pomalyst)
• DVT risk
– Proteosome inhibitors (Velcade, Kyprolis)
– Chemotherapy (MP, VAD, Doxil, HyperCVAD)
– Supportive care
• Bisphosphonates
Myeloma Treatment
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
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)
Waldenstrom’s
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
Case #2
• 73yo WF presenting with neuropathy,
dizziness, 40lb weight loss, IgM 5454,
immediately hospitalized due to neurologic
symptoms, started plasma exchange
Case #2
• Bone Marrow
– Bone marrow, flow cytometric immunophenotypic
analysis: Monoclonal plasma cells and
lymphocytes identified, consistent with
Waldenstrom's macroglobulinemia.
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
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
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
Amyloidosis
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
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
Questions
Miten R. Patel, MD
Office 904-516-3737
Cell phone 904-451-9820
[email protected]