# Multiorgan Failure Resembling Grade 5 (Fatal) Cytokine Release Syndrome in Patient with Multiple Myeloma Following Carfilzomib Infusion: A Case Report

## TL;DR

A patient with multiple myeloma died after developing severe multiorgan failure resembling cytokine release syndrome following a third dose of Carfilzomib.

## Contribution

Reports a rare fatal case of Carfilzomib-induced multiorgan failure resembling cytokine release syndrome.

## Key findings

- A 74-year-old male with multiple myeloma died within 24 hours of developing grade 5 multiorgan failure after the third Carfilzomib infusion.
- Symptoms included fever, tachycardia, hypotension, hypoxia, and encephalopathy, resembling cytokine release syndrome.
- Infectious causes were ruled out, suggesting Carfilzomib as the likely trigger for the fatal reaction.

## Abstract

Background: Cytokine release syndrome (CRS) is a life-threatening systemic inflammatory condition marked by excessive cytokine production, leading to multi-organ dysfunction. It is commonly associated with T-cell-engaging therapies such as chimeric antigen receptor (CAR) T cells, T-cell receptor bispecific molecules, and monoclonal antibodies. Carfilzomib, a proteasome inhibitor, is known to cause a range of adverse effects, primarily hematologic and cardiovascular. However, multiorgan failure grade 5 (fatal), resembling CRS has not been previously reported in association with Carfilzomib. Case Report: A 74-year-old male with relapsed multiple myeloma developed grade 5 multiorgan failure 60 min after the third dose of Carfilzomib, resulting in death within 24 h of symptom onset. The patient tolerated the first doses of Carfilzomib well with only fever and headache developing post infusion. Before the second dose, the patient developed worsening pancytopenia, prompting the discontinuation of Lenalidomide. After the second Carfilzomib infusion, he experienced fever and transient encephalopathy, which resolved with acetaminophen, corticosteroids, and supportive care. However, following the third dose, he rapidly deteriorated—developing fever, tachycardia, hypotension, hypoxia, and encephalopathy. Despite aggressive management with intravenous fluids, broad-spectrum antibiotics, corticosteroids, and tocilizumab, the patient progressed to refractory shock and multi-organ failure, culminating in death within 24 h. A comprehensive infectious workup was negative, ruling out sepsis and suggesting possible Carfilzomib-induced CRS. Conclusion: Grade 5 multiorgan failure with signs and symptoms similar with CRS following Carfilzomib administration is a rare but potentially fatal adverse drug reaction. Further research is needed to better define the risk factors and optimal management strategies for Carfilzomib-induced multiorgan failure and possible CRS.