Salivary gland swelling as a characteristic manifestation of local cytokine release syndrome after anti-CD19 chimeric antigen receptor T cell therapy: A case series

Cytokine release syndrome (CRS) is the most common adverse event of chimeric antigen receptor T (CAR-T) cell therapy and is usually characterized by systemic symptoms such as fever, hypotension, and hypoxia. However, there have been several recent reports of local CRS characterized by cervical swelling. This localized syndrome can cause life-threatening laryngeal edema and requires early diagnostic treatment. Here we report 3 cases of local CRS where bilateral salivary gland swelling emerged following anti-CD19 CAR-T cell therapy for relapsed or refractory diffuse large B-cell lymphoma. Following tocilizumab treatment for systemic CRS, all patients exhibited cervical swelling. Physical examinations revealed significant swelling of the bilateral submandibular glands, and computed tomography scans showed substantial enlargement of the bilateral parotid and submandibular glands. Immediate treatment with dexamethasone effectively managed the potentially life-threatening laryngeal or pharyngeal edema, thereby preventing severe airway obstruction. This study has demonstrated, for the first time to our knowledge, that salivary gland enlargement is a common finding in local CRS. This observation suggests that physicians should continue to closely monitor the risk of developing cervical edema leading to life-threatening airway obstruction after systemic CRS, even in patients treated with tocilizumab. If salivary gland swelling is observed, it would be better to consider prompt evaluation and dexamethasone administration.