Efficacy and safety of venetoclax in relapsed/refractory chronic lymphocytic leukemia in Russia routine clinical practice

Background. Chronic lymphocytic leukemia (CLL) is a slowly progressive malignant disease that results in uncontrolled proliferation and accumulation of B-lymphocytes in the blood and bone marrow, and is the most common form of leukemia in Western countries. Patients with CLL and chromosome 17 deletion or TP53 mutation who progress after treatment with immunological, chemotherapeutic, and targeted agents (e. g., ibrutinib) have a poor prognosis and represent a population with an unmet medical need. Clinical trial results have shown that venetoclax, a selective, bioavailable, orally administered inhibitor of the anti-apoptotic B-cell lymphoma protein, induces apoptosis in CLL cells and provides an alternative treatment option for CLL patients, either alone or in combination with rituximab.

Aim. To evaluate the efficacy and safety of venetoclax in relapsed/refractory CLL in Russia routine clinical practice.

Materials and methods. A multicenter observational prospective study P19-569 FORTE was conducted in Russia. The patients were monitored throughout the 24-month treatment period. During this period, the treating physician assessed the objective treatment response according to the International CLL Working Group criteria. The last minimal residual disease result obtained during treatment and the method of its assessment (if performed) were also to be recorded. The primary endpoint was the overall response rate at 12 months after initiation of treatment.

Results. The study included 71 previously treated patients with relapsed/refractory CLL. The median age was 63 (35–83) years. All patients were white/Caucasian, and the majority were male. According to baseline characteristics, the study population included patients who had previously received intensive therapy: the median number of previous therapy lines was 3 (1–8). A number of factors associated with the risk of an unfavorable prognosis have been identified in patients, including chromosome 17 deletion or TP53 mutation.

12 months after the start of treatment, the overall response rate was 68.6 %, complete remission was observed in 41.4 % of patients; in the venetoclax monotherapy subgroup these parameters were 63.3 and 42.9 %, in the venetoclax with ibrutinib subgroup – 81.0 and 38.1 %, respectively. 24 months after the start of treatment, the overall response rate was 71.4 %, complete remission was observed in 45.7 % of patients; in the venetoclax monotherapy subgroup these parameters were 67.3 and 46.9 %, in the venetoclax with ibrutinib subgroup – 81.0 and 42.9 %, respectively. During 24 months of treatment, minimal residual disease was assessed in 28 (40 %) patients, of whom 14 (50 %) had undetectable disease in the peripheral blood or bone marrow.

There were 23 deaths during the study. The median overall survival was not achieved. No laboratory signs of tumor lysis syndrome were detected in patients. The majority of adverse events leading to death were CLL progression; the 2nd largest group were cases of SARS-CoV-2 infection.

Conclusion. The obtained data confirm the possibility of venetoclax therapy in relapsed/refractory CLL patients.

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