CLL Coverage from Every Angle

Gene Mutations and Risk of Infection: Report From LRF CLL4 Trial

By: Emily Rhode
Posted: Wednesday, May 26, 2021

Specific gene mutations appear to increase the risk of death from infection in patients with chronic lymphocytic leukemia (CLL), according to the results of a recent study published in the journal Leukemia. Mutations in the BRAF, FBXW7, NRAS, and XPO1 genes seemed to be associated with death from infection in patients participating in the LRF CLL4 clinical trial. Patients who received two or more lines of treatment for CLL were also at a higher risk of death from infection.

“Careful management of infection risk, including appropriate choice of CLL therapeutic agents and prophylaxis against infection, may be important in patients who carry one or more of these mutations,” wrote Daniel Catovsky, MD, of The Institute of Cancer Research, London, and colleagues.

The data from 777 patients with previously untreated CLL enrolled in the multicenter randomized LRF CLL4 trial were analyzed. Of the 600 patients whose cause of death was known, 258 (43%) died of infection. The patients who died of infection were more likely than those who died of other causes to have received two or more lines of treatment (194/258 [75%] versus 231/342 [68%], P = .04). Infection was the cause of death in 46 of 67 patients (69%) with available mutation data who had a mutation of one or more of the BRAF, FBXW7, NRAS, and XPO1 genes versus 129 of 333 patients (39%) with no mutations of these genes (odds ratio = 3.46 [95% confidence interval = 1.98–6.07], P < .0001).

Study limitations included the small number of patients with each of the gene mutations, a lack of data on treatments received by patients after the end of clinical follow-up in 2010, and the end of the general use of randomized treatments in LRF CLL4. Future studies may examine whether deaths from infection follow similar patterns now that BCR and BCL2 inhibitors are in clinical use.

Disclosure: The authors reported no conflicts of interest.

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