Objective:

To increase awareness of immune-mediated chemotherapy side effects

Background:

Durvalumab is an immune checkpoint inhibitor (ICI) chemotherapeutic drug enhancing immune anti-cancer response by inhibiting PD-L1 and promoting T-cell activation. Paraneoplastic limbic encephalitis (LE) is a syndrome characterized by cross-reactive autoimmune response to the limbic structures usually preceding diagnosis of malignancy. Definitive treatment of LE is the treatment of cancer, however, interplay between immunotherapy used for cancer treatment and paraneoplastic conditions brings diagnostic and management challenges.

Design/Methods:

Not applicable

Results:

A 57-year-old woman with small cell lung cancer initially treated with cisplatin, etoposide, and radiation therapy was subsequently transitioned to Durvalumab. Three days after starting Durvalumab, she developed severe global aphasia. Brain MRI demonstrated restricted diffusion in the left posterior temporal lobe with cortical and subcortical T2/FLAIR hyperintensity and mild leptomeningeal enhancement. EEG showed near continuous lateralized rhythmic delta activity in the left hemisphere. Serum ANNA-1(Anti-Hu) antibodies titer was 1:30720. The patient was diagnosed with Anti-Hu antibody medicated LE. Durvalumab was discontinued. Improvement in reading, writing and word finding abilities was noted after a 5-day plasmapheresis. Follow up serum ANNA-1(Anti-Hu) titer was 1:256; EEG normalized; and MRI brain showed decreased left posterior temporal cortical swelling and FLAIR hyperintensity with decreased enhancement.

Conclusions:

This is a first documented case of Durvalumab potentially inducing ANNA-1(Anti-Hu) mediated limbic encephalitis, likely due to the enhancing preexisting immune cells harboring ANNA-1(Anti-Hu) antibodies at baseline titers too low to induce clinical manifestations. This case suggests it may be helpful to obtain paraneoplastic panel prior to starting immune therapy for cancers, and to monitor patients for development of paraneoplastic syndromes while treating patients with Durvalumab.