The number of signaling pathways affected by mutations may be important for prognostic purposes in patients with chronic lymphocytic leukemia (CLL), according to a recent study presented in Clinical Cancer Research.

Risk stratification in patients diagnosed with CLL is often based on the use of the CLL-International Prognostic Index (CLL-IPI). However, there may be genetic patterns with prognostic value beyond what is provided using the CLL-IPI.

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In this single-center study based in Denmark, researchers performed genetic sequencing and cytogenetic analyses on cells from 314 patients with newly diagnosed CLL. The primary outcomes presented in this report were overall survival (OS) and time to first treatment (TTFT).

Initial CLL-IPI risk status was available for 291 patients, of whom 57% were classified as having low risk. Intermediate risk was identified for 30% of patients, 11% showed high risk, and 2% were considered to have very high risk.

Median follow-up was 6.5 years, at which point 31% of the cohort had died, and 37% had been treated for CLL with a median TTFT of 14.2 months (interquartile range, 2.4-35.2).

From 56 analyzed genes, 515 mutations were found overall. A total of 70% of patients showed mutations, and there were 17 genes with mutations in more than 2% of patients. More than half of the patients (53%) possessed driver mutations, which were linked to poorer OS and a shorter TTFT.

TTFT was affected by the number of altered genetic pathways, regardless of CLL-IPI risk status at the time of diagnosis. The number of driver mutations itself was less prognostic of TTFT compared with the number of affected pathways.

The researchers suggested analyzing a panel of 25 driver genes for prognostic use in CLL. “We propose to include the number of pathways altered by driver mutations together with CLL-IPI in prospective studies of CLL from time of diagnosis for possible incorporation into clinical care and personalized follow-up and treatment,” the researchers concluded.

Reference

1.     Brieghel C, da Cunha-Bang C, Yde CW, et al. The number of signaling pathways altered by driver mutations in chronic lymphocytic leukemia impacts disease outcome [published online January 9, 2020]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-18-4158