The leading cause of death for patients with chronic lymphocytic leukemia (CLL) is infections. The overall survival of patients with CLL has improved in recent decades, but the risk of death from infection hasn’t changed.

Carefully managing risk of infection, particularly for patients with certain genetic mutations, may be important for patients with CLL, according to research published in Leukemia.

The LRF CLL4 trial followed patients for a median of 13 years, providing long-term data on the cause of death of 600 of 777 patients. Baseline molecular data was available for 499 patients as well.


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The authors sought to understand what factors may increase patients’ risk for infection and death. The study compared patients who died of infection with all other patients who died during the follow-up period.

The data from the LRF CLL4 trial included cause of death for 600 patients. 43% (n=258) of patients died from infection. Infections included pneumonia (67%), sepsis (38%), and opportunistic infections (11%).

A total of 43% of patients died during first-, second- or third-line treatment, while 57% of patients died off treatment. Patients who died of infection were more likely to have undergone 2 or more lines of treatment.

BRAF, FBXW7, NRAS, and XPO1 mutations and 11q deletion were most significantly associated with death from infection in 400 patients with a known cause of death and available gene mutation data. 47 of 162 (29%) patients with 11q deletion died of infection versus 40 of 209 (19%) without the deletion (P =.03).  69% of patients who had a mutation in 1 or more of the 4 genes (46 out of 67 patients) died from infection compared with 39% without a mutation (129 out of 333) (P <.0001).

The median overall survival in the trial was 6 years, and was similar for patients who died of infection and those who died of other causes. In the LRF CLL4 clinical trial, patients with BRAF and NRAS mutations had shorter overall survival.

Patients with CLL who have received 2 or more lines of treatment or have at least one of these mutations may need close monitoring for infection.

Reference

Else M, Blakemore SJ, Strefford JC, Catovsky D. The association between deaths from infection and mutations of the BRAF, FBXW7, NRAS and XPO1 genes: a report from the LRF CLL4 trial. Leukemia. 2021;1-7. doi:10.1038/s41375-021-01165-w