Effect of Statins in the Watch and Wait Phase of Chronic Lymphocytic Leukemia

Abstract

Background: It is an unclear how cholesterol-lowering statin drugs affect progression of chronic lymphocytic leukemia (CLL).

Methods: Clinical records of 57 CLL patients were examined to determine how initiating statins in the "watch and wait" phase of management affected disease progression.

Results: After 6.4 ± 0.6 months, when average low-density lipoprotein cholesterol levels had been lowered from 3.58 ± 0.11 mM to 2.1 ± 0.06 mM, blood levels of CLL cells and beta-2-microglobulin (β2M) increased significantly, accompanied by significant decreases in platelets. Following statin institution, rates of change of blood lymphocytes and β2M increased from 1.55 ± 0.39 × 10⁶ to 3.4 ± 0.68 × 10⁶ cells/mL/month (n = 43) and 0.035 ± 0.011 to 0.055 ± 0.007 μg/mL/month (n = 40), respectively. Conventional first-line CLL treatment was ultimately required in 37 patients.

Conclusions: These observations suggest that statins as single agent do not slow and may even modestly stimulate progression of CLL.

Keywords: STAT3; chronic lymphocytic leukemia; lipoproteins; statins.

FIGURE 1

Markers of CLL progression after statin institution. Clinical records of 57 patients (26 female and 31 male) who commenced statins between 2012 and 2023 in the “watch and wait” phase of management with documented serial LDL measurements, were examined. Records of 19 patients with progressive disease (eventually requiring first‐line therapy) and 21 patients with benign disease (with no evidence of disease progression after prolonged follow‐up) that also had multiple recorded LDL measurements were used as controls. (A) Temporal changes in lymphocytes, β2M, and LDL cholesterol are shown for Patient 11 treated with simvastatin (left panel) and patient P17, who progressed to first‐line therapy but was never exposed to statins (right panel). Note the inflection point indicated by the vertical line seen shortly after starting simvastatin. (B) Lymphocytes, platelets, and β2M values were recorded prior to starting the statin and after the LDL cholesterol had dropped near 2.1 mM. Averages and standard errors of the differences are shown for patients with U‐CLL and patients with M‐CLL. IGHV mutation status was not available for three patients. (C, D) Rates of change of lymphocyte numbers (C) and β2m levels (D) before and after statins were calculated from the difference in these parameters divided by the time in months between the two measurements for 43 and 40 patients, respectively, where these rates could be reliably calculated. Rates for benign and progressor patients not treated with statins were calculated before and after a spontaneous inflection point. Otherwise, “early” and “late” results were the rate changes observed over the entire observation period. The results are consistent with mild progression of CLL following institution of statins. *, p < 0.05. statistical analysis was done by Student t‐tests or ANOVA.