1136 - Serum Monoclonal Immunoglobulin Predicts Inferior Prognosis in Patients Treated for Chronic Lymphocytic Leukemia

Introduction: The prognostic significance of monoclonal immunoglobulins/paraproteins in patients with chronic lymphocytic leukemia (CLL) remains incompletely understood. Previous studies have primarily focused on the importance of paraprotein at the time of CLL diagnosis. In a recent Italian study, Corbigni et al. (Br J Haematol 2020) found that the presence of serum monoclonal immunoglobulin (MIg) at CLL diagnosis was linked to a worsened prognosis. However, the prognostic significance of MIg in patients at the time of initiation of therapy has not been investigated.

Objectives: This single-centre, retrospective study aimed to examine the presence and prognostic relevance of serum MIg in patients with CLL. We included all patients diagnosed with CLL fulfilling the IWCLL criteria with available result of MIg testing at the beginning of their CLL treatment. Serum paraprotein detection was performed using automated serum protein and immunofixation electrophoresis. We performed statistical analyses with the R software (version 4.2.1, www.r-project.org). Differences in proportion were determined using the chi-squared test. Survival curves were constructed using the Kaplan–Meier method, and differences in survival were compared via the log-rank test. Independent predictors of time to event were determined by Cox regression analysis.

Results: A total of 220 consecutive patients treated for CLL between 1996 - 2022 were included in this study. Among the patients, 42 (19%) exhibited detectable serum MIg, with 23 (55%) having IgM paraprotein and 19 (45%) having IgG paraprotein. Full details of baseline demographic and clinical characteristics are presented in Table 1. The median follow-up period was 102 months, the estimated overall survival from the start of first-line treatment was 92 months (95% Confidence interval [CI], 65-119) in patients without the presence of MIg vs. 78 months (95% CI, 61-94) in those with detectable MIg (Fig. 1 ). In univariate analysis, the presence of paraprotein was associated with a shortened overall survival from first-line treatment (hazard ratio [HR] of 1.48 (95% CI 1.02-2.17; p=0.04). Additionally, shorter overall survival was shown in patients treated with chemoimmunotherapy who did not receive targeted inhibitors during their clinical course (HR 1.72 (95% CI 1.08-2.74; p=0.02), in participants aged > 65 years (HR 2.69, 95% CI 1.80-4.02; p < 0.001). Treatment without oral kinase inhibitors and age over 65 maintained their importance in multivariate analysis. Moreover, TP53 deletion/mutation was associated with inferior outcomes (HR 2.95, 95% CI 1.01-8.59, p=0.05) in multivariate analysis.

Conclusion: The presence of serum paraprotein in patients with chronic lymphocytic leukemia emerged as a negative prognostic marker for patients initiating first-line therapy. Further studies are needed to confirm these findings.