Milestones in Chronic Lymphocytic Leukemia

Rákkutatás · Chronic lymphocytic leukemia · TP53

Targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors and BCL‑2/PI3Kδ inhibitors improve progression‑free survival in chronic lymphocytic leukemia patients, including those with high‑risk genetic aberrations.

Treatment decisions for patients with chronic lymphocytic leukemia (CLL) are dependent on symptoms and classification into high-, medium-, or low‑risk categories. The prognosis for CLL hinges, in part, on the presence or absence of less‑favorable genetic aberrations, including del(17p), del(11q), TP53 dysfunction, and IGHV mutations, as these markers are associated with worse treatment response. Promising results from multiple clinical trials show emerging therapies targeting Bruton tyrosine kinase, B‑cell leukemia/lymphoma 2, and phosphatidylinositol 4,5‑bisphosphate 3‑kinase catalytic subunit delta result in better outcomes and prolonged progression‑free survival for patients both with and without certain high‑risk aberrations. Favorable outcomes using these novel oral targeted therapies, either alone or in combination with other treatments such as anti‑CD20 antibodies, have led to their use almost entirely supplanting chemoimmunotherapy in the treatment of CLL. In this narrative review, we summarize the current clinical evidence for the use of targeted mono‑ and combination therapies for CLL, discuss new and next‑generation treatment approaches currently in development, and provide insight into areas of unmet need for the treatment of patients with CLL.

These targeted agents represent a paradigm shift from cytotoxic chemoimmunotherapy to precise molecular inhibition, providing superior efficacy and tolerability even in patients harboring adverse genetic lesions that historically predict poor response to standard therapy.

Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.

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