31.3.2. Prognostic value of sFLCs and HLCs in DLBCL

Chapter 31

Maurer et al. [662] evaluated the prognostic utility of sFLC measurements in two large independent cohorts of untreated DLBCL patients (N0489: n=76 and MER: n=219). sFLC measurements were similar in the two cohorts (Figure 31.5). Patients with elevated sFLCs (i.e. a κ and/or λ sFLC concentration above the normal range) had inferior EFS and OS compared to patients with normal sFLCs (both cohorts p<0.02) (Figure 31.6) [662]. The prognostic significance of elevated sFLCs persisted for a total of 6 years of follow-up [16]. Elevated sFLCs remained significantly associated with reduced OS and EFS after adjusting for the International Prognostic Index in both the N0489 (both p<0.02) and MER (both p<0.001) cohorts[662]. The prognostic utility of elevated sFLCs has been confirmed in other studies [663][696][697].

Witzig et al. [664] reported that although DLBCL patients with monoclonal sFLC elevations tended to have poorer prognosis compared with that of patients with polyclonal sFLC elevations, this did not reach statistical significance. Moreover, monoclonal sFLCs predicted for ABC-type DLBCL: in all, 73% of patients with monoclonal sFLC elevations were of ABC-type (by the Hans algorithm) compared with 33% of patients with normal sFLCs [664]. By contrast, polyclonal elevations or normal sFLCs were not associated with a particular molecular subtype.

Elevated sFLCs were more common in patients with elevated serum creatinine (58%) than in patients with normal creatinine (29%) [662]. Interestingly, the association of elevated sFLCs and poor outcome was strengthened in the subset of patients with normal creatinine (n=241, OS Hazard Ratio 4.09, p<0.001), while there was no association of elevated creatinine with outcome (n=40, OS Hazard Ratio 1.00 p>0.60). This suggests that the association of sFLCs with outcome was not related to renal impairment.

Jardin et al. [663] studied the prognostic utility of HLC analysis in a cohort of 409 DLBCL patients enrolled on the LNH03-B clinical trial program of the French GELA study. Abnormal IgMκ/IgMλ HLC ratios and IgGκ/IgGλ HLC ratios or elevated IgMκ or IgMλ were each associated with significantly unfavourable outcomes. For example, patients with abnormal IgMκ/IgMλ HLC ratios had a 5-year OS of 50.8% compared with 78.1% for patients with normal IgM HLC ratios (p=0.0003, Figure 31.7). In multivariate analysis, which included six sFLC and HLC variables identified in univariate analysis, only an abnormal IgMκ/IgMλ HLC ratio remained predictive of progression-free survival (PFS) and OS. In a separate multivariate model, including IgMκ/IgMλ HLC ratio and IPI score, the IgMκ/IgMλ HLC ratio remained predictive of PFS (p=0.03).

The prognostic value of IgM HLC was also confirmed by Johansson et al. [919], who studied 187 patients with aggressive lymphoma, of which DLBCL accounted for the majority (67.9%) of cases. An abnormal IgMκ/IgMλ ratio was observed in 20% of patients, and was associated with adverse clinical characteristics including advanced Ann Arbor stage (p=0.005), high international prognostic index (p=0.001) and extranodal disease (p=0.003). An abnormal IgMκ/IgMλ ratio also predicted a shorter time to treatment failure and OS, and remained prognostic on multivariate analysis.