Article of the week: The role of serum IgM levels as a predictor of symptomatic hyperviscosity in Waldenström’s macroglobulinaemia (WM)

This week’s Article of the Week is a study that was recently published in the British Journal of Haematology on the role of serum IgM levels as a predictor of symptomatic hyperviscosity in Waldenström’s macroglobulinaemia (WM).

Gustine et al’s paper ‘Serum IgM level as predictor of symptomatic hyper viscosity in patients with Waldenström macroglobulinaemia’ is based on the premise that identifying asymptomatic patients at high risk of symptomatic hyperviscosity may help prevent catastrophic events by allowing clinicians to begin treatment earlier. It also focuses on determining a specific IgM threshold at which this level of risk might become an indication for treatment. The authors performed a retrospective review of 825 patients diagnosed with WM in one clinic from 1999 to 2016 and identified 113 cases of symptomatic hyperviscosity (defined as recurrent epistaxis, new-onset headaches, new-onset blurry vision, slowed mentation, and/or presence of retinal vessel changes or haemorrhage). They also collected a range of other data including serum IgM levels, haemoglobin levels, bone marrow biopsies and the presence of specific genetic mutations.

The results showed that the median serum IgM level at the time of symptomatic hyper viscosity was 61.8g/L (range 31-124) and that the cumulative incidence increased from 10.8% at 12 months from diagnosis up to 26% at 120 months. The median time from diagnosis to the development of symptomatic hyperviscosity was shortened with higher serum IgM levels being only 3 months for those with serum IgM levels higher than 60g/L and 156 months for those with serum IgM levels of 30-40g/L. No patient in their group experienced symptomatic hyperviscosity with serum IgM levels less than 30g/L. The crude incidence of symptomatic hyperviscosity also increased with serum IgM levels ranging between only 3% of patients for levels from 30-40g/L up to 67% for those with levels higher than 60g/L (370-fold higher odds).

The authors also found that other factors increased the risk of symptomatic hyperviscosity. These included anaemia with haemoglobin level less than 115g/L at diagnosis, more than 50% bone marrow involvement at diagnosis and age less than 65 years at diagnosis. Additionally, this study found that the odds of symptomatic hyperviscosity were significantly higher for patients found to have a CXCR4 nonsense mutation (OR 4.94), whereas the MYD88 mutation had no effect on risk. Other factors that did not affect the level of risk included gender, platelet count, serum beta-2 microglobulin levels, cryoglobulins or cold agglutinins.

The study also looked at the management and outcomes of patients with symptomatic hyperviscosity. The intervention of choice to address hyperviscosity was emergent plasmapheresis until WM-directed therapy can take effect. All patients who received treatment (112) experienced resolution of their symptoms. Looking at overall survival, there was no difference observed between those patients who experienced symptomatic hyperviscosity from those who did not.

In this study, a serum IgM level of at least 30g/L was identified as the threshold at which patients with WM become at risk of developing symptomatic hyperviscosity. The authors suggest this as a threshold where increased monitoring and regular fundoscopic examination is indicated at a minimum. The authors also suggest that with approximately two thirds of patients with serum IgM levels more than 60g/L going on to develop symptomatic hyperviscosity within months, this should be the threshold where WM-directed therapy is almost certainly indicated. Although the survival data showed that those who develop symptomatic hyperviscosity do not have worse outcomes overall, in some instances hyperviscosity related injury is irreversible and therefore should be prevented wherever possible.

Please see the link to the full article here