Predictive significance of selected gene mutations in relapsed and refractory chronic lymphocytic leukemia patients treated with ibrutinib

• Published in: European journal of haematology Vol. 106; no. 3; pp. 320 - 326
• Main Authors: Machnicki, Marcin M., Górniak, Patryk, Pępek, Monika, Szymczyk, Agnieszka, Iskierka‐Jażdżewska, Elżbieta, Steckiewicz, Paweł, Bluszcz, Aleksandra, Rydzanicz, Małgorzata, Hus, Marek, Płoski, Rafał, Makuch‐Łasica, Hanna, Nowak, Grażyna, Juszczyński, Przemysław, Jamroziak, Krzysztof, Stokłosa, Tomasz, Puła, Bartosz
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2021
• Subjects: ATM mutations; Bruton's tyrosine kinase; Chronic lymphocytic leukemia; Egr-2 protein; Enzyme inhibitors; ibrutinib; Kinases; Leukemia; Lymphatic leukemia; Medical prognosis; Mutation; next‐generation sequencing; p53 Protein; Patients; Survival; TP53 mutations; ibrutinib; TP53 mutations; chronic lymphocytic leukemia; ATM mutations; next-generation sequencing
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.13550

Background Ibrutinib, an inhibitor of the Bruton's kinase (BTK), is characterized by high efficacy in the therapy of patients with relapsed and refractory chronic lymphocytic leukemia (RR‐CLL). Aims To analyze the potential significance of the mutational status of selected 30 genes on the disease outcome in 45 patients with RR‐CLL using custom‐made gene panel and sequencing on Illumina MiSeq FGx platform. Results The highest rate of mutations was observed in 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%). With a median observation time of 45.9 months, the median progression‐free survival (PFS) and overall survival (OS) were not reached. The 36‐month estimated rate of PFS and OS were 64% and 68.2%, respectively. The overall response rate was noted in 23 patients (51.1%), while twenty (44.4%) patients achieved stability. Progression was noted in 2 (4.5%) cases. Analyzed molecular factors had no impact on PFS and OS. Conclusion 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.