Increasing karyotypic complexity is independently associated with inferior survival in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib, according to a study published in Blood.

The researchers noted that complex karyotype (defined as 3 or more cytogenetic abnormalities) is known to be an adverse prognostic factor in patients with relapsed or refractory CLL who are treated with ibrutinib or venetoclax.

However, the researchers sought to determine whether increasing karyotypic complexity, treated as a continuous variable, could serve as a prognostic indicator of survival for CLL patients treated with ibrutinib.

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The researchers retrospectively evaluated 456 CLL patients treated with ibrutinib alone or in combination with an anti-CD20 antibody. Prior to ibrutinib, the patients had received a median of 2 therapies (range, 0-13).

Half of patients had 3 or more cytogenetic abnormalities, and 30% had more than 5. Three-quarters of patients had IGHV-unmutated disease, and 30% had del(17p).

Multivariable analysis indicated that increasing karyotypic complexity was an independent predictor of shorter progression-free survival (hazard ratio [HR], 1.07; 95% CI, 1.04-1.10; P <.0001) and overall survival (HR, 1.09; 95% CI, 1.05-1.12; P <.0001).

In addition, the presence of clonal evolution at disease progression, as determined by cytogenetic analysis, was prognostic of subsequent survival (P =.02).

“This solidifies karyotypic complexity as an important prognostic factor for CLL patients treated with ibrutinib,” the researchers wrote. “Further research should consider sequential karyotypic analysis as a determination of the risk of progression and death in patients with CLL.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Kittai AS, Miller CR, Goldstein D, et al. The impact of increasing karyotypic complexity and evolution on survival in CLL patients treated with ibrutinib. Blood. Published online July 27, 2021. doi:10.1182/blood.2020010536