Prediction of Treatment Efficacy in Relapsed Chronic Lymphocytic Leukemia

Abstract

Background. The emergence of signaling pathway inhibitors (SPI) considerably improved the prognosis in relapsed chronic lymphocytic leukemia (R-CLL). Nevertheless, some patients cannot achieve optimal and sustained response. TP53 gene defects determine the refractoriness to immunochemotherapy (ICT) and lower rates of progression-free survival on SPI therapy. However, the prognostic value of complex karyotype (CK) in CLL has long been disputed. In recent years, greater attention has been placed on the prognostic impact of CK in the context of SPI therapy. Materials & Methods. The study included 180 patients who received the drug treatment for R-CLL (113 of them with ICT, 67 of them with SPI). Their age at the onset of second-line therapy, the response to first-line therapy, early (< 24 months) progression after first-line therapy, the number of therapy lines, and the presence of CK and TP53 gene defect were regarded as prognostic markers. Taking into account the clonal evolution in CLL, to assess the significance degree of the above predictors, Cox proportional hazards regression model with time-dependent variables was used. Results. The following independent factors proved to significantly reduce the risk of death: response achieved immediately after first-line therapy (hazard ratio [HR] 0.38; 95% confidence interval [95% CI] 0.20-0.72; p = 0.003) and the number of therapy lines (HR 0.56; 95% CI 0.37-0.86; p = 0.008). Treatment with only ICT in first and subsequent lines was associated with increasing risk of death (HR 2.25; 95% CI 1.09-4.63; p = 0.028). Genetic risks worsened the prognosis to a high degree of significance in the case of TP53 gene defect with excluded or unknown CK status (HR 10.54; 95% CI 4.25-26.17; p < 0.001) as well as in the case of CK (HR 14.08; 95% CI 5.77-34.35; p < 0.001). A significant predictor of poor outcome was reported to be the factor of unknown CK status without TP53 gene defect (HR 4.15; 95% CI 1.72-10.00; p = 0.002). Neither relapse time after first-line therapy nor the age > 65 years showed independent prognostic value. Conclusion. Standard karyotyping of peripheral lymphocytes with specific stimulation establishes a clearer disease prognosis and suggests the optimal choice of R-CLL treatment strategy.