(070) Catatonia following Autologous Tumor-Infiltrating Immunotherapy and IL-2 Infusions: A Case Report

Abstract:

Background:

While there are many examples of catatonia associated with autoimmune conditions and encephalitis, few articles have recorded associations with immunotherapy treatments. We describe a case of catatonia following Autologous Tumor-Infiltrating Immunotherapy (TIL) and Interleukin-2 (IL-2) therapies.




Case:

AB is a 59-year-old male with a history of depression and recurrent metastatic oropharyngeal carcinoma who underwent an eight-day protocol that included lymphodepletion, then infusion with TIL and six doses of IL-2. He appeared close to baseline at discharge, but developed increasingly bizarre behavior that evening. He was brought to the emergency department and found to be hypertensive to 170/60s, tachycardic to 170s, and afebrile, and was observed self-dialoguing with repetitive movements and freezing. Medical and neurological workup were noncontributory, though he was initiated on IV dexamethasone for suspicion for immunotherapy neurotoxicity. Psychiatry was consulted on hospital day two for altered mental status. On evaluation, he scored 16 on the Bush-Francis Catatonia Rating Scale for symptoms of immobility, mutism, staring, posturing, echolalia, verbigeration, negativism, waxy flexibility, and withdrawal. A lorazepam trial of 2 mg IV was initiated and showed a partial response. He was started on scheduled lorazepam titrated to 1.5mg three times daily with significant improvement. After several days, he was close to his cognitive baseline and was discharged on a lorazepam taper. He improved back to his usual baseline and was tapered off lorazepam over a few months without recurrence in catatonia symptoms.




Discussion:

This case highlights catatonia as a potential adverse effect from TIL and IL-2 Infusions in cancer treatment. The temporal proximity of symptom onset to the infusions supports a potential connection. There is a known association between aberrations in pro-inflammatory cytokines and psychiatric illness, including soluble IL-2 receptors (Goldsmith, 2016). In general, an elevation in pro-inflammatory cytokines can result in a hypoactive motor state, such as catatonia, and the neurotoxic effects of an inflammatory response may be responsible for the catatonic state (Rogers, 2019). However, systemic inflammation would represent an unusual mechanism as most non-psychiatric presentations of catatonia are related to infectious or autoimmune processes (Rogers, 2019). AB did not respond to systemic steroids and medical workup did not indicate an infectious etiology. Other notable points in this case are AB’s lack of past psychiatric history, aside from mild depression, and the sudden onset of symptoms with quick resolution.




Conclusion:

To our knowledge, this case uniquely describes catatonia as an adverse event associated with TIL and IL-2 therapies and potentially implicates cancer-focused immunotherapy in general. As it only depicts a single event, the generalizability of risk for catatonia associated with these therapies is unclear. However, the rapid improvement in symptoms and effectiveness of treatment with lorazepam alone is encouraging for future cases.