Variations of the ataxia telangiectasia mutated gene in patients with chronic lymphocytic leukemia lack substantial impact on progression-free survival and overall survival: a Cancer and Leukemia Group B study

Abstract

The impact of mutation of the ATM (ataxia telangiectasia mutated) gene in chronic lymphocytic leukemia (CLL) treatment outcome has not been examined. We studied ATM mutations in 73 patients treated with fludarabine and rituximab. ATM gene mutation analysis was performed using temperature gradient capillary electrophoresis. The impact of detected variants on overall survival (OS) and progression-free survival (PFS) was tested with proportional hazards models. None of the 73 patients demonstrated truncating ATM mutations; 17 (23%, 95% confidence interval 14–35%) had non-silent variants (ATM-NSVs), including 13 known ATM polymorphisms and four missense variants. ATM-NSVs were not significantly associated with any baseline characteristics including immunoglobulin heavy chain variable gene (IGVH) status. In multivariable models, no significant differences in complete response (p =0.70), PFS (p =0.59) or OS (p =0.13) were observed. Our data indicate that truncating ATM mutations are rare in patients with CLL. Furthermore, in this dataset, these non-silent variants had limited impact on PFS and OS.

Keywords::

• Chronic lymphocytic leukemia
• ATM mutation
• prognosis
• chemoimmunotherapy

Acknowledgements

This work was supported in part by National Cancer Institute grants CA31946 to the Cancer and Leukemia Group B (CALGB), CA33601 to the CALGB Statistical Center and P50 CA140158 to J.C.B., and the D. Warren Brown Family Foundation.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.