Are Clinical Outcomes Affected by Genetic Mutations in Ibrutinib-Treated CLL?
Posted: Thursday, February 11, 2021
According to research presented in the European Journal of Haematology, patients with chronic lymphocytic leukemia (CLL) who undergo treatment with the Bruton’s kinase inhibitor ibrutinib may experience extended clinical benefit despite the presence of genetic mutations associated with a poor prognosis. Bartosz Pula, MD, PhD, of the Institute of Hematology and Transfusion Medicine in Warsaw, and colleagues analyzed survival outcomes associated with the mutational status of 30 genes.
The study included 45 patients with relapsed and refractory CLL who had undergone a significant number of previous treatments. Gene analysis was performed using a custom-built gene panel, and the Illumina MiSeq FGx platform supported sequencing. Mutations were found to be most common across 13 genes: TP53 (n = 18; 40.0%), NOTCH1 (n = 13; 28.8%), SF3B1 (n = 11; 24.4%), ATM (n = 7; 15.6%), MED12 (n = 6, 13.3%), CHD2 (n = 5; 11.1%), XPO1 (n = 5; 11.1%), NFKBIE (n = 5; 11.1%), BIRC3 (n = 4; 8.9%), SPEN (n = 4; 8.9%), POT1 (n = 4; 8.9%), EGR2 (n = 3; 6.7%), and RPS15 (n = 3; 6.7%).
At a median follow-up of 45.9 months, 44.4% of patients (n = 20) had achieved disease stability, and the overall response rate was 51.1% (n = 23). Disease progression occurred in 4.5% of patients (n = 2). The median and 36-month estimated progression-free survival rates were not reached and 65%, respectively, whereas the median and 36-month estimated overall survival rates were not reached and 68.2%, respectively.
“Despite accumulation of several poor prognostic factors in our real‐life cohort of heavily pretreated patients with CLL, ibrutinib treatment showed long‐term clinical benefit,” the study authors concluded.
Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.
