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Vol. 20, Art. 20 (pp. 229-241)    |    2019       

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The efficacy of targeted drugs as a remedy for eradication and control of residual tumor clone in patients with chronic lymphocytic leukemia

Voloshin S.V., Kuvshinov A.Yu., Bessmeltsev S.S., Mikhaleva M.A., Garifullin A.D., Krivolapov Yu.А., Belyakova Е.А., Bubnova L.N., Rugal V.I., Bogdanov A.N., Chechetkin A.V.

Brief summary

The use of combinations of modern drugs for treatment of chronic lymphocytic leukemia (CLL) helps to achieve deeper and longer remissions. Nevertheless, residual tumor cells may remain in the patients body, which has reached even complete remission, which is the minimal residual disease (MRD). From a clinical point of view, the assessment of the MRD of CLL has proved its independence as a prognostic marker of survival. The standardized and most frequently used methods for assessing the residual tumor clone in CLL are multicolor flow cytometry (FC) and an allele-specific polymerase chain reaction (aPCR) of immunoglobulin heavy chains (IGHV). Monitoring residual tumor cells is of particular scientific interest given the possibility of the emergence of MRD-adapted therapy for CLL. Aim. Assessment the status of minimal residual disease in patients with chronic lymphocytic leukemia who received targeted drugs in treatment programs. Materials and Methods. The study evaluating the effectiveness of ibrutinib and venetoclax in patients with CLL included 85 patients who achieved remission of the disease after an induction treatment program. Group 1 (n = 28) - patients receiving therapy with the inclusion of ibrutinib and / or venetoclax. Group 2 (n = 57) - patients who received standard chemotherapy (BR, FCR). MRD assessment was performed using 4-color PCR on bone marrow (BM) samples. Results. During the study, significant differences in the frequency of achieving MRD-negative status between groups were not revealed: 17.9% and 29.8%, respectively (p> 0.05). The progression rate in group 1 was 10.7%, and in group 2 it was 63.2% (p = 0.00001). When analyzing PFS indicators, statistically significant differences were identified. The median PFS in patients from group 1 was not achieved, and in patients from group 2 it was 45.9 months. (p = 0,0007). Conclusion. In the era of targeted drugs, the treatment of CLL undergoes revolutionary changes, thereby changing the place and importance of chemoimmunotherapy. It has been demonstrated that the addition of targeted drugs to standard immunochemotherapy programs can improve the effectiveness of treatment. Thus, along with long-term control of the disease, especially desirable for the elderly group of patients, MRD-negative remission is becoming a realistic prospect for patients with CLL.


Key words

chronic lymphocytic leukemia, minimal residual disease, targeted therapy, ibrutinib, venetoclax.

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