WM Flashcards
Typical immunophenotype WM:
CD19+, CD20+, sIgM+
CD5, CD10, CD23 may be positive in 10%– 20% of cases and does not exclude diagnosis.
Studies have shown that mutations in this gene are found in up to 40% of patients with
Waldenström macroglobulinemia (WM)/LPL and can impact ibrutinib response.
CXCR4 gene mutation
Retinal examination should be done if
- IgM ≥3.0 g/dL or
- If hyperviscosity is suspected
Indications for treatment in WM
- Hyperviscosity
- Neuropathy
- Organomegaly
- Amyloidosis
- Cold agglutinin disease
- Cryoglobulinemia
- Anemia and other cytopenias associated with disease
- Bulky adenopathy
- B symptoms
- Cytopenias
Components of Asymptomatic Waldenström macroglobulinemia (WM) risk score:
- Bone marrow involvement (%)
- Serum IgM level (mg/dL)
- Serum beta-2 microglobulin level (mg/L)
- Serum albumin level (g/dL)
Follow-up for asymptomatic WM include CBC, CMP,
SPEP, serum immunoglobulins:
- Low Risk
- Intermediate Risk
- High Risk
Follow-up for asymptomatic WM include CBC, CMP,
SPEP, serum immunoglobulins:
- Low Risk: 12 months
- Intermediate Risk: 6 months
- High Risk: 3 months
Asymptomatic or minimally symptomatic WM
Retinal examination once a year if serum IgM level ________ mg/dL.
Consider therapy in asymptomatic patients with serum IgM level _____ mg/dL.
> 3000 mg/dL
> 6000 mg/dL
Should be performed for patients with symptomatic hyperviscosity, and before treatment with rituximab-containing regimen in patients with IgM ≥4000 mg/dL.
Plasmapheresis
Red blood cell (RBC) transfusion, if indicated, should be done after plasmapheresis to prevent added hyperviscosity load.
Proposed Criteria for the Diagnosis of Waldenström Macroglobulinemia
- IgM monoclonal gammopathy of any concentration
- Bone marrow infiltration by small lymphocytes, plasmacytoid cells, and plasma cells
- Diffuse, interstitial, or nodular pattern of bone marrow infiltration
- CD19+, CD20+, sIgM+; CD5, CD10, CD23 can be expressed in some cases of Waldenström macroglobulinemia and does not exclude diagnosis.
REVISED IPSS WALDENSTRÖM MACROGLOBULINEMIA SCORING SYSTEM
- Age <65 0
- Age 66–75 1
- Age >75 2
- B2 microglobulin >4 mg/L 1
- LDH >250 IU/L 1
- Serum albumin <3.5 g/dL 1
Score Stage
0 Very Low
1 Low
2 Intermediate
3 High
4–5 Very High
Drug that can potentially cause cardiac and pulmonary toxicity, especially in older patients
Carfilzomib
TRUE OR FALSE
Serial serum IgA and IgG levels should be carefully monitored as these can be depleted with WM therapies.
TRUE
Serial serum IgA and IgG levels should be carefully monitored as these can be depleted with WM therapies.
Preferred Primary Therapy for WM
- Bendamustine/rituximab
- Bortezomib/dexamethasone/rituximab
- Ibrutinib ± rituximab (category 1)
- Zanubrutinib (category 1)
Regimen that can be considered for patients presenting with symptomatic hyperviscosity, or in whom rapid IgM reduction is required
Bortezomib/dexamethasone/rituximab
Rapid increases in IgM levels (IgM rebound) have been observed following discontinuation of:
BTK inhibitors
Consider continuing therapy with the BTK inhibitor until starting the next line of therapy or monitor for IgM rebound after discontinuation of BTK inhibitors.
May be used for rituximab-intolerant individuals as a single agent or in combination therapy anywhere that rituximab is given
Ofatumumab
Neurological deficits concerning Bing Neel syndrome:
- Headaches
- Seizures
- Cranial nerve palsies
- Weakness in limbs
- Atypical neuropathy
Essential diagnostics for Bing Neel syndrome:
- Brain and entire spine MRI with gadolinium enhancement
- Lumbar puncture for cerebrospinal fluid (CSF) analysis (cytology, multiparameter flow cytometry, PCR for IgH gene rearrangement, PCR for MYD88 L265P)
Useful in Certain Circumstances
* Biopsy of affected tissue
* Concurrent bone marrow aspiration and biopsy for IgH gene rearrangement and MYD88 L265P testing
Preferred Regimens for Symptomatic Bing Neel syndrome:
- Ibrutinib
- Zanubrutinib
