Recent BCMA-directed therapies have shown promise in treating RRMM, but they also bring a unique concern: neurotoxicity.

We present a descriptive case series involving two patients who developed refractory immune effector cell-associated neurotoxicity syndrome (ICANS) and one patient develop Guillain Barre Syndrome (GBS) after temclistamab infusion. 

In two cases, a 64-year-old male (Patient A) and a 66-year-old female (Patient B), both treated with teclistamab developed ICANS not responsive to toxicity mitigation strategies. Patient A completed a cycle of teclistamab and developed ICANS grade 1 on day eight which worsened to ICANS grade 3 on day 12 even with treatment with dexamethasone and anakinra. Patient B received the first dose of teclistamab and within hours of infusion developed hemodynamic collapse and cognitive impairment consistent with ICANS grade 1. The patient was started on dexamethasone; however, did not respond and required vasopressors. Unfortunately, her ICANS worsened on day eight. On day 12, treatment was escalated to intrathecal hydrocortisone and anakinra and subsequently to methylprednisolone 1g. Unfortunately, both patients passed away due to the progression of the disease. Another patient developed GBS after one dose of the medication. The lower extremity paralysis has improved after treatment with steroids and IVIG.

Treatment with teclistamab, has led to unexpected, refractory ICANS and neurotoxicity. Despite employing a range of interventions, disease progression was observed, ultimately resulting in the death of both patients. It's vital to highlight that, in both of these patients, despite experiencing severe ICANS, imaging did not reveal any abnormalities. This contrasts with prior literature findings associating ICANS with T2/FLAIR parenchymal hyperintensity, cerebral edema in imaging. Both cases emphasize the need for early detection to mitigate the consequences of ICANS in patients undergoing similar therapies.