Waldenström macroglobulinemia

Figures & data

Table 1. Definitions of IgM-related phenomenon in macroglobulinemia (adapted from Gertz et al. PMID 21874060)

	IgM monoclonal component	Symptoms of tumor mass/infiltration (adenopathy anemia)	Marrow infiltration >10%	IgM-mediated symptoms
MGUS	+	−	−	−
Smoldering macroglobulinemia	+	−	+	−
IgM-related disorder (e.g. cold agglutinin hemolytic anemia, type II cryoglobulin, neuropathy, amyloidosis)	+	−	±	+
Macroglobulinemia	+	+	+	±

Note: IgM, immunoglobulin M; MGUS, monoclonal gammopathy of undetermined significance.

Table 2. Diagnostic approach to suspected Waldenström macroglobulinemia

• Serum protein electrophoresis

• Serum immunofixation to validate the immunoglobulin M (IgM) heavy chain and the type of light chain

• Quantitative test for immunoglobulin G, immunoglobulin A, and IgM

• 24-hour urine collection for protein electrophoresis. Monoclonal light chains are detected in the urine of 40–80% of patients tested

• Immunoglobulin free light chain assay

• Serum beta2-microglobulin evaluation for prognosis; part of the international staging system for Waldenström macroglobulinemia

• Bone marrow biopsy. Intertrabecular monoclonal lymphoplasmacytic infiltrate ranges from predominantly lymphocytic cells to overt plasma cells

• Cytogenetic studies with optional fluorescence in situ hybridization

• Computed tomography of abdomen and pelvis to detect organomegaly and lymphadenopathy (a skeletal survey and radiographic imaging of the bones are unnecessary in the absence of symptoms; lytic bone lesions are unusual)

• Serum viscosity required when signs and symptoms of hyperviscosity syndrome are present or when IgM>4000 mg/dl

• On the basis of clinical presentation, analysis involves Coombs test (cold autoantibody) and cryoglobulin or tissue stains for amyloid deposits

• Of myeloma patients, 1% have IgM, and their disorder behaves like other multiple myeloma

Table 3. ISSWM: International Staging System for Waldenström macroglobulinemia factors associated with prognosis in the IWMSS

• Age>65
• Hemoglobin<11·5 g/dl
• Platelet count<100 K/microliters
• B2-microglobulin>3 mg/dl
• Monoclonal IgM concentration>7 g/dl
Risk category	Factors	Median survival (months)
Low	0 or 1 (except age)	142·5
Intermediate	Age >65 or 2	98·6
High	>2	43·5

Note: Morel P. et al. Blood. 2009;113(18):4163–70.

Table 4. DRC regimen

• Dexamethasone 20 mg IV day 1
• Rituximab 375 mg/m^2 IV day 1
• Cyclophosphamide 100 mg/m^2 PO BID days 1–5 (total dose 1000 mg/m^2)
DRC courses are repeated every 21 days for 6 courses
• N = 72
• CR = 7%
• PR = 67%	ORR = 83%
• MR = 9%
• SD = 8%
• PD = 8%
Median time to 50% IgM reduction was 4·1 months (range 0·7–14)IgM flare in 32%, >25% IgM increase in 11%

Note: Dimopoulos M.A. et al. J Clin Oncol. 2007;25(22):3344–9.

Figure 1. M-SMART algorithm for newly diagnosed Waldenström.

Figure 2. M-SMART algorithm for relapsed Waldenström.