33.4. Prognostic value of combined FLC measurements

Chapter 33

Summated κ + λ sFLCs (ΣFLC) is a measure of both monoclonal tumour cell and polyclonal “bystander” FLC production. Morabito et al. [675] studied the prognostic utility of ΣFLC in 449 untreated CLL patients. After a median follow-up of 3 years, 33% of patients had received treatment. Receiver operating characteristic (ROC) analysis defined an optimal cut-off of ΣFLC (60.6 mg/L) that identified patients with inferior outcome. The percentages of patients not requiring treatment at 3 years were 84.1% and 51.8% for patients with ΣFLC ≤60.6 mg/L or >60.6 mg/L, respectively (Figure 33.4A). A further study by Sarris et al. [676] confirmed that baseline ΣFLC >60 mg/L were associated with shorter TTFT, and also demonstrated that ΣFLC >60 mg/L correlated with shorter OS. Morabito et al. [675] demonstrated that on multivariate analysis, ΣFLC >60.6 mg/L, ZAP-70 expression, cytogenetic abnormalities, and Binet stage B+C remained significantly associated with inferior TTFT. The prognostic significance of ΣFLC >60.6 mg/L was significantly higher than the sFLC κ/λ ratio, with a 3-fold higher risk of early treatment requirement for patients with ΣFLC >60 mg/L compared to those with an abnormal κ/λ sFLC ratio (hazard ratios of 3.5 [p<0.0001] versus 1.5 [p=0.015]).

Morabito et al. [675] proposed a novel prognostic scoring system was proposed in which ΣFLC >60.6 mg/L, ZAP-70 expression, cytogenetic abnormalities and Binet stage were combined [675]. In this model, 1 point was assigned for each unfavourable marker present. The percentages of patients not requiring treatment at 3 years were 94.8%, 84.5%, 61.6% and 21.1% for patients scoring 0, 1, 2 or 3/4 respectively (p<0.0001) (Figure 33.4B). The authors concluded that the cumulative amount of ΣFLC, irrespective of their clonality, represents a strong and independent prognostic predictor in CLL. An alternative CLL risk-stratification model that incorporates ΣFLC concentrations and Hevylite immunoparesis was proposed by Tadmor et al. [1203].