Management strategies for patients with chronic lymphocytic leukaemia harbouring complex karyotype

Abstract

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease characterised by the uncontrolled proliferation of mature lymphocytes. A subset of CLL patients harbouring complex karyotype (CK) presents with poor prognosis and limited treatment options. This review aims to discuss the current understanding of such patient subset, including its molecular landscape, diagnostic approaches, treatment modalities and emerging therapies. Furthermore, it outlines strategies for personalised management to improve clinical outcomes in this challenging patient population.

Keywords: BTK inhibitors; chronic lymphocytic leukaemia; complex karyotype (CK); high‐CK cytogenetic complexity; novel therapies; venetoclax.

FIGURE 1

Hypothetical model illustrating a possible evolutionary pathway of genome instability of CLL clones over time. (A) Genomic instability and mutational events such as telomere dysfunction, chromothripsis and previous exposure to radiation lead to the expansion of clones with a survival advantage; (B) treatment start: Therapies (e.g. chemotherapy, targeted therapy) temporarily reduce disease burden but select for resistant clones; (C) even if the disease is under control, genomic complexity can increase, complicating treatment due to the emergence of highly resistant clones. According to the data provided by the literature, clonal evolution is more significant in patients treated with chemo‐immunotherapy and continuous therapy with BTKi., , ,

FIGURE 2

Possible treatment pathways for patients with CLL‐carrying CK. Currently, there are no official guidelines on the optimal therapeutic strategy for this high‐risk patient group. BsAbs, bispecific antibodies; cBTKi, covalent BTK inhibitor; CIT, chemio‐immunotherapy; I + V, ibrutinib plus venetoclax; ncBTKi, non‐covalent BTK inhibitor; VenG, venetoclax plus obinutuzumab; VenR, venetoclax plus rituximab.