B-cell Receptor Pathway Mutations Are Infrequent in Patients with Chronic Lymphocytic Leukemia on Continuous Ibrutinib Therapy

* Purpose: Acquired mutations in Bruton’s tyrosine kinase (BTK) were more common in patients with relapsed/refractory CLL. or phospholipase C-g2 (PLCG2) genes are associated with clinical Median time to first detection of BTK C481S mutation was not progressive disease (PD) in patients with chronic lymphocytic reached in previously untreated patients and was >5 years in leukemia (CLL) treated with BTK inhibitors. Data on mutation patients with relapsed/refractory CLL. Among patients evaluable rates in patients without PD on ibrutinib treatment are limited. at PD, previously untreated patients (n ¼ 12) had lower rates than Experimental Design: We evaluated frequency and time to those with relapsed/refractory disease (n ¼ 45) of BTK (25% vs. detection of BTK and PLCG2 mutations in peripheral blood samples 49%) and PLCG2 mutations (8% vs. 13%). Time from first detection from 388 patients with previously untreated (n ¼ 238) or relapsed/ of BTK C481S mutation to PD was 11.3 months in 1 previously refractory (n ¼ 150) CLL across five clinical trials. untreated patient and median 8.5 months (range, 0–35.7) among 23 Results: With median follow-up of 35 months (range, 0–72) patients with relapsed/refractory CLL. without PD at last sampling, mutations in BTK (3%), PLCG2 (2%), Conclusions: This systematic investigation describes develop- or both genes (1%) were rare in previously untreated patients. With ment of mutations over time in patients without PD and informs the median follow-up of 35 months (range, 1–70) without PD at last potential clinical opportunity to optimize ongoing benefits for such sample, mutations in BTK (30%), PLCG2 (7%), or both genes (5%) patients.