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Karyotypic Complexity and Evolution May Impact Survival of Ibrutinib-Treated Patients With CLL

By: Celeste L. Dixon
Posted: Wednesday, August 25, 2021

The results of a large retrospective analysis published in Blood lend further support to the conclusion that increased karyotypic complexity may be independently associated with inferior survival for patients with chronic lymphocytic leukemia (CLL) treated with the kinase inhibitor ibrutinib. Karyotype evolution that has occurred at the time of disease progression on ibrutinib therapy also may predict inferior survival in this population, wrote Jennifer A. Woyach, MD, of The James Comprehensive Cancer Center at The Ohio State University, Columbus, and colleagues.

The researchers evaluated records of 456 patients treated between 2010 and 2019 with either single-agent ibrutinib or an ibrutinib/anti-CD20 antibody combination at The James, whether they were treatment-naive or had relapsed or refractory disease. Of all patients, 50% had a complex karyotype, defined as the presence of at least three cytogenetic abnormalities, and 30% had at least five cytogenetic abnormalities. In addition, 30% of patients had del(17p), and 75% had IGHV-unmutated disease; overall, the patients had a median of two prior therapies.

Multivariable analysis indicated that increasing karyotypic complexity, treated as a continuous variable, independently predicted shorter progression-free survival (P < .0001) and overall survival (P < .0001). “Presence of clonal evolution determined by cytogenetic analysis at progression was [also] prognostic of [worse] subsequent survival (P = .02),” the authors stated.

The interplay among karyotypic complexity, del(17p), and IGHV mutational status appears to be complicated, they concluded. These results “show that del(17p) is strongly associated with complex karyotype defined as at least five abnormalities.” However, “although del(17p) was highly prognostic as a singular variable, it did not provide additional significant prognostic value when [a] complex karyotype was accounted for. Thus, when [a] karyotype is not available, del(17p) can be very helpful, but when a karyotype is available, complexity data may provide more valuable prognostic information,” the study authors noted.

Disclosure: The study authors’ disclosure information can be found at ashpublications.org.



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