A new study has found that B-cell receptor pathway mutations are rare in patients with chronic lymphocytic leukemia (CLL) on continuous ibrutinib therapy.
The results were published in Clinical Cancer Research in a paper by Jennifer Woyach, MD, of the Ohio State University Comprehensive Cancer Center, and colleagues.
Acquired mutations in Bruton’s tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease in patients with CLL treated with BTK inhibitors, but until now there was little data on mutation rates in patients without progressive disease on ibrutinib treatment.
The researchers evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 CLL patients, of whom 150 were relapsed or refractory, across five clinical trials.
With a median follow-up of 35 months without progressive disease at last sampling, mutations in BTK (3%), PLCG2 (2%) or both genes (1%) were rare in previously untreated patients. For patients with relapsed or refractory CLL, mutations in BTK (30%), PLCG2 (7%), or both genes (5%) were more common.
Median time to first detection of the BTK C481S mutation was not reached in previously untreated patients and was greater than five years in patients with relapsed or refractory CLL. Among patients evaluable at progressive disease, previously untreated patients (n=12) had lower rates than those with relapsed or refractory disease (n=45) of BTK (25% vs 49%) and PLCG2 mutations (8% vs 13%).
The time from first detection of the BTK C481S mutation to progressive disease was 11.3 months in one previously untreated patient and median 8.5 months (range, 0-35.7 months) among 23 patients with relapsed or refractory CLL.
“This systematic investigation describes development of mutations over time in patients without [progressive disease] and informs the potential clinical opportunity to optimize ongoing benefits for such patients,” the authors wrote.
Woyach JA, Ghia P, Byrd JC, et al. B-cell receptor pathway mutations are infrequent in patients with chronic lymphocytic leukemia on continuous ibrutinib therapy [published online ahead of print, 2023 Jun 14]. Clin Cancer Res. 2023; CCR-22-3887. doi:10.1158/1078-0432.CCR-22-3887