18.4.5. Discrepancies between HLC and IFE during follow-up

Chapter 18

Ludwig et al. [37] observed a normal HLC ratio in 12 of 35 MM patients who achieved a near complete response (nCR: 100% monoclonal protein reduction by electrophoresis, but IFE-positive), or a very good partial response (VGPR: at least 90% serum and urine monoclonal protein reduction) following treatment. This discrepancy between HLC analysis and IFE may be due to the recovery of polyclonal immunoglobulins producing a normal HLC ratio, despite the persistence of small amounts of monoclonal immunoglobulin. While continuing low levels of a monoclonal protein may reflect residual disease, it has been shown that a normal HLC ratio predicts a good patient outcome, irrespective of IFE positivity (Chapter 20).

In IgG patients specifically, persistence of small amounts of monoclonal IgG is partly the result of a prolonged half-life due to recycling by FcRn receptors, causing IFE to remain positive after the tumour has been eradicated. This is an issue previously reported by Waldmann et al. [102] (Chapter 3) and demonstrated in Figure 18.15. Consistent with this, discrepancies between IFE and bone marrow immunophenotypic responses can be observed during follow-up [407].

HLC ratios are not affected by the variable metabolism of IgG and for the detection of residual disease, they demonstrate a better agreement than sIFE with flow cytometry results (Figure 18.16) [421]. Others have similarly found a good correlation between HLC and flow cytometry during serial monitoring [411] including those patients treated with novel agents [978].