Prolonged immune checkpoint inhibitor response of a patient with a RET rearranged non-small cell lung cancer and high tumour mutational burden: Case report and review of the literature

Patients with oncogenic driven metastatic non-small cell lung cancer (NSCLC) represent a special subgroup of metastatic NSCLC, as for several oncogenic drivers, tyrosine kinase inhibitors (TKI, either registered or within a trial) are available. One of the more challenging drivers to target is the rearranged during transfection (RET) fusion, initially found in thyroid cancers, but also present in 1-2% of NSCLC patients. Initially, RET was targeted with multi-kinase inhibitors, with fairly disappointing results (generally no long-term responses and high rates of adverse effects). Selective TKIs are currently being investigated, and results are promising. Limited data is available regarding immune checkpoint inhibitor (ICI) efficacy in NSCLC patients with a RET rearrangement. We present a case of a male patient with stage IV NSCLC with a RET gene rearrangement, with low programmed death-ligand 1 (PD-L1) expression, but high tumour mutational burden (TMB), responding to second line nivolumab. To put these data into perspective, we also review the literature regarding treatment of NSCLC patients with a RET gene rearrangement with either TKIs or ICI.