B-cell Receptor Pathway Mutations Are Infrequent in Patients with Chronic Lymphocytic Leukemia on Continuous Ibrutinib Therapy
Woyach, Jennifer A. (The Ohio State University Comprehensive Cancer Center, Columbus, Ohio)
Ghia, Paolo (Universita Vita-Salute San Raffaele, Milan, Italy)
Byrd, John C. (University of Cincinnati College of Medicine, Cincinnati, Ohio)
Ahn, Inhye E. (Laboratory of Lymphoid Malignancies, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland)
Moreno, Carol (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Brien, Susan M. (UC Irvine. Chao Family Comprehensive Cancer Center, Irvine, California)
Jones, Daniel (The Ohio State University Comprehensive Cancer Center, Irvine, California)
Cheung, Leo W.K. (Pharmacyclics LLC, an AbbVie Company, South San Francisco, California)
Chong, Elizabeth (Pharmacyclics LLC, an AbbVie Company, South San Francisco, California)
Kwei, Kevin (Pharmacyclics LLC, an AbbVie Company, South San Francisco, California)
Dean, James P. (Pharmacyclics LLC, an AbbVie Company, South San Francisco, California)
James, Dannelle F. (Pharmacyclics LLC, an AbbVie Company, South San Francisco, California)
Wiestner, Adrian (Laboratory of Lymphoid Malignancies, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland)

Date:	2023
Abstract:	Purpose: Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited. Experimental design: We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients with previously untreated (n = 238) or relapsed/refractory (n = 150) CLL across five clinical trials. Results: With median follow-up of 35 months (range, 0-72) without PD at last sampling, mutations in BTK (3%), PLCG2 (2%), or both genes (1%) were rare in previously untreated patients. With median follow-up of 35 months (range, 1-70) without PD at last sample, mutations in BTK (30%), PLCG2 (7%), or both genes (5%) were more common in patients with relapsed/refractory CLL. Median time to first detection of BTK C481S mutation was not reached in previously untreated patients and was >5 years in patients with relapsed/refractory CLL. Among patients evaluable at PD, previously untreated patients (n = 12) had lower rates than those with relapsed/refractory disease (n = 45) of BTK (25% vs. 49%) and PLCG2 mutations (8% vs. 13%). Time from first detection of BTK C481S mutation to PD was 11. 3 months in 1 previously untreated patient and median 8. 5 months (range, 0-35. 7) among 23 patients with relapsed/refractory CLL. Conclusions: This systematic investigation describes development of mutations over time in patients without PD and informs the potential clinical opportunity to optimize ongoing benefits for such patients.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Clinical Cancer Research, Vol. 29 Núm. 16 (august 2023) , p. 3065-3073, ISSN 1557-3265

DOI: 10.1158/1078-0432.CCR-22-3887
PMID: 37314786

9 p, 442.2 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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