Next Generation Sequencing Reveals Potentially Actionable Alterations in the Majority of Patients with Lymphoid Malignancies

JCO Precis Oncol. 2017 Jun;1:PO.16.00004. doi: 10.1200/PO.16.00004. Epub 2017 Apr 27.

Abstract

Next generation sequencing (NGS) identifies alterations that may be potentially targetable by Food and Drug Administration (FDA) approved drugs and/or by available experimental agents that may not have otherwise been contemplated. Many targeted drugs have been developed for diverse solid cancers; a smaller number of genomically targeted drugs have been approved for lymphoid malignancies. We analyzed NGS results from 60 patients with various lymphoid malignancies and found a total of 224 alterations (median per patient = 3). Forty-nine patients (82%) had potentially actionable alterations using FDA-approved drugs and/or experimental therapies; only 11 patients (18%) had no theoretically actionable alterations. Only three patients (5%) had an alteration for which an approved drug in the disease is available (on-label); 45 patients (75%) had an alteration for which an approved drug is available in another disease (off-label). The median number of alterations per patient potentially actionable by an FDA-approved drug was 1. Interestingly, 19 of 60 patients (32%) had intermediate to high tumor mutational burden, which may predict response to certain immunotherapy agents. In conclusion, NGS identifies alterations that may be pharmacologically tractable in most patients with lymphoid malignancies, albeit with drugs that have usually been developed in the context of solid tumors. These observations merit expanded exploration in the clinical trials setting.

Keywords: Next generation sequencing; lymphoid malignancies; precision medicine.