Encephalopathy Post CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma: Beyond ICANS

Area of Science:

• Oncology
• Infectious Diseases
• Immunology

Background:

• Chimeric antigen receptor T-cell (CAR-T) therapy is a promising treatment for hematologic malignancies.
• Human herpesvirus 6 (HHV-6) reactivation is a rare but severe complication post-CAR-T therapy.
• HHV-6 reactivation can present with symptoms overlapping immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), complicating diagnosis.

Purpose of the Study:

• To describe a case of HHV-6 reactivation in a multiple myeloma patient undergoing CAR-T therapy.
• To highlight the diagnostic challenges posed by overlapping symptoms of HHV-6 reactivation and ICANS.
• To emphasize the importance of early virologic testing and prompt antiviral intervention.

Main Methods:

• A case report of a 68-year-old male with relapsed/refractory multiple myeloma treated with CAR-T therapy.
• Clinical presentation, diagnostic workup including CSF and plasma PCR, and treatment interventions were documented.
• Radiological findings (brain MRI) and patient outcomes were analyzed.

Main Results:

• The patient developed CRS and ICANS, followed by recurrent encephalopathy and neurological decline.
• Initial evaluations were negative, but repeat testing confirmed HHV-6 reactivation.
• Despite antiviral therapy and supportive care, the patient experienced progressive neurological decline and multiorgan failure, ultimately succumbing to the illness.

Conclusions:

• HHV-6 reactivation is a critical, underrecognized cause of neurotoxicity following CAR-T therapy.
• Overlapping clinical and radiological features with ICANS can obscure the diagnosis of HHV-6 reactivation.
• Maintaining a high index of suspicion for HHV-6 reactivation in patients with delayed or atypical neurotoxicity is essential for timely diagnosis and potential improvement of outcomes.