Predicting Patient Outcomes in CLL

Chronic lymphocytic leukemia (CLL) cell in blood flow - super closeup view 3d illustration: ©LASZLO - stock.adobe.com

CXC chemokine ligand 13 (CXCL13) and galectin-9 plasma levels can be effective prognostic biomarkers to predict time to first treatment (TTFT) and progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), according to a study performed at Sohag University in Cairo, Egypt.¹

Patients with CLL who showed high CXCL13 and galectin-9 levels had advanced clinical stages, poor prognosis, shorter PFS, shorter TTFT, and higher therapy resistance. Soluble CXCL13 and galectin-9 levels also demonstrated good specificity and sensitivity in identifying CLL disease progression.

“By directly evaluating these biomarkers before therapy and analyzing follow-up results over a long 4 years, we noticed that high initial levels of these biomarkers were associated with a higher predictive ability of short TTFT and were correlated with unfavorable treatment responses, suggesting that these biomarkers may be a better predictor of CLL treatment responses,” study authors wrote.¹

The study enrolled 91 newly diagnosed and treatment-naïve patients with CLL, and 50 sex-and age-matched healthy volunteers were used as controls. Serum CXCL13 and galectin-9 levels were notably higher in patients with CLL compared with controls. The median serum CXCL13 and galectin-9 levels were 118.0 pg/mL (range, 40.0-1290.0 pg/mL) and 653.0 pg/mL (range, 300.0-2315.0 pg/mL), respectively, in patients with CLL. Comparatively, the healthy volunteers had a median CXCL13 concentration of 39.5 pg/mL (range, 25.0-250.0 pg/mL) and a median galectin-9 concentration of 274.5 pg/mL (range, 160.0-450.0 pg/mL; P <.0001).

Furthermore, patients with advanced stage (III or IV) CLL had higher CXCL13 levels than patients with stage I or II disease, and galectin-9 levels were higher in patients with stages II, III, or IV disease compared with patients with stage I disease.

Regarding PFS, patients with a galectin-9 level ≥ 650 pg/mL (P =.004) and a CXCL13 level ≥ 120 pg/mL (P =.005) had worse PFS outcomes. For TTFT, patients with low plasma concentrations of CXCL13 (<120 pg/mL) had a median TTFT of 24 months (95% CI, 0.5-42 months; n = 46; P = .0001). Conversely, patients with high CXCL13 concentrations (≥ 120 pg/mL) had a median TTFT of 4 months (95% CI, 0-27 months; n = 45). Moreover, the median TTFT for patients with high galectin-9 levels (≥ 650 pg/mL) was also 4 months (95% CI, 0-27 months; n = 47). This compared with a median TTFT of 23 months for patients with low galectin-9 levels (<650 pg/mL; 95% CI, 0.5-43 months; n = 44; P <.0001).

Patients with anemia and/or thrombocytopenia had higher plasma concentrations of CXCL13 and galectin-9. Additionally, a negative correlation was observed between CXCL13 levels and platelet count. However, there was no association noted between CXCL13 and galectin-9 concentrations and level of bone marrow infiltration.

The median patient age was 61 years (range, 50-80), and 59.3% of patients were male. All patients met the immunophenotypic and clinical criteria for CLL. Patients were excluded from the study if they had additional malignancies, acute inflammatory disorders, or histories of kidney, liver, or heart failure.

These findings help to bolster a systematic review and metanalysis published earlier this year that identified high galectin expression as a poor prognostic predictive marker in hematologic cancers.²

“Galectin-9 and CXCL13 can be combined to create more useful indicators for directing CLL clinical practice. Our study highlights the impact of galectin-9 and CXCL13 as crucial prognostic markers for CLL patients,” study authors concluded.¹

REFERENCES:

1. Ahmed HA, Nafady A, Ahmed EH, et al. CXC chemokine ligand 13 and galectin-9 plasma levels collaboratively provide prediction of disease activity and progression-free survival in chronic lymphocytic leukemia [published online ahead of print, 2023 Nov 9]. Ann Hematol. 2023;10.1007/s00277-023-05540-8. doi:10.1007/s00277-023-05540-8

2. Liu H, Dai Q, Li Y, Tang Z, She T. Association between high galectin expression and poor prognosis in hematologic cancers: a systematic review and meta-analysis. Hematology. 2023;28(1):2227494. doi:10.1080/16078454.2023.2227494