Immune Checkpoint Inhibitor Therapy for Periocular Merkel Cell Carcinoma.

We herein report four patients with periocular Merkel cell carcinoma treated with immune checkpoint inhibitors who experienced a dramatic response and, therefore, had less morbid surgery and/or avoided radiation therapy with its inherent ocular toxicity.

Disruption of adenosine metabolism increases risk of seizure-induced death despite decreased seizure severity.

OBJECTIVE: Respiratory arrest plays an important role in sudden unexpected death in epilepsy (SUDEP). Adenosine is of interest in SUDEP pathophysiology due to its influence on seizures and breathing. The objective of this investigation was to examine the role of adenosine in seizure severity, seizure-induced respiratory disruption, and seizure-induced death using mouse models. Understanding adenosinergic contributions to seizure cessation and seizure-induced death may provide insights into how SUDEP can be prevented while avoiding increased seizure severity. METHODS: Our approach was to examine: (1) seizure severity and seizure-induced death after 15 mA electroshock seizures and during repeated pentylenetetrazol (PTZ) administration in wild-type mice (Adk+/+) and transgenic mice with reduced adenosine metabolism (Adk+/-); (2) the postictal hypercapnic ventilatory response (HCVR) in wild-type mice (the postictal HCVR could not be examined in Adk+/- mice due to their high mortality rate); and (3) the effects of adenosinergic drugs on seizure severity and seizure-induced death following maximal electroshock (MES). RESULTS: Adk+/- mice were more vulnerable to seizure-induced death in the 15 mA electroshock and repeated PTZ models. Despite increased mortality, Adk+/- mice had comparable seizure severity in the PTZ model and reduced seizure severity in the 15 mA electroshock model. Breathing and HCVR were suppressed by 15 mA electroshock seizures in wild-type mice. Pharmacological inhibition of adenosine metabolism decreased MES seizure severity but did not increase mortality. A1 selective and nonselective adenosine receptor antagonists increased seizure-induced death following MES. SIGNIFICANCE: Adenosine has opposing effects on seizure severity and seizure-induced death. On the one hand, our seizure severity data highlight the importance of adenosine in seizure suppression. On the other hand, our mortality data indicate that excessive extracellular adenosine signaling can increase the risk of seizure-induced respiratory arrest.

Immune checkpoint inhibitors with or without chemotherapy for orbital, conjunctival, and ocular adnexal squamous cell carcinoma.

OBJECTIVE: Periocular squamous cell carcinoma (SCC) is relatively rare and presents unique anatomic considerations due to proximity to the eye and risk to ocular structures associated with high-dose radiation therapy or radical surgery. We present our observations in patients with periocular SCC treated with immune checkpoint inhibitor (ICI) therapy in an effort to decrease surgical morbidity or avoid high-dose radiation therapy. METHODS: Retrospective review of patients with orbital, conjunctival, or periocular SCC who were treated with ICI either in the neoadjuvant setting prior to surgery or for treatment of perineural spread in the orbit/skull base. RESULTS: Twelve men and 5 women with orbital (n = 6), conjunctival (n = 5), or lacrimal sac/duct (n = 2) SCC, or SCC with perineural spread (n = 4) were treated with ICI (cemiplimab or pembolizumab) either as single drug (n = 9) or combined with chemotherapy (n = 8). Overall, 5 patients achieved complete response, 8 patients achieved partial response, and 4 patients achieved stable disease, using the response evaluation criteria in solid tumors (RECIST) criteria. The objective response rate was 76.5%. In 12 patients ICI was used in the neoadjuvant setting prior to surgery. In 4 patients with perineural spread and unresectable disease, ICI was used to avoid high-dose radiation therapy. One additional patient with conjunctival SCC with nodal metastasis was treated with ICI alone and achieved a dramatic complete response and has thus far managed to avoid surgery altogether. CONCLUSIONS: ICI either as single drug or in combination with chemotherapy has a high response rate in patients with periocular SCC. Future prospective trials should aim to correlate molecular data with response.

Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.

Successful Treatment of Refractory Orbital Plasmacytoma with Chimeric Antigen Receptor T Cell Therapy: A Case Report and Review of the Literature.

Orbital plasmacytoma is a rare plasma cell tumor that may arise as an aggressive form of extramedullary multiple myeloma. Treatment modalities include surgical excision, radiation, and chemotherapy. Chimeric antigen receptor T cell therapy is currently reserved for refractory disease. The authors present a case of a 69-year-old woman with an extensive orbital plasmacytoma refractory to multimodal therapy who was treated with idecabtagene vicleucel chimeric antigen receptor T cell therapy. Four days after infusion, the patient exhibited grade 1 cytokine release syndrome, which resolved with tocilizumab. The orbital plasmacytoma significantly decreased in size 1 month after treatment and demonstrated complete serological response and sustained tumor burden reduction at 10-month follow-up. This case highlights the efficacy of chimeric antigen receptor T cell therapy for refractory orbital plasmacytoma and calls attention to potential inflammatory toxicities.