How can neurotoxicity associated with CAR T-cell therapy in MM be managed?

The Multiple Myeloma Hub spoke with Peter Forsberg, Colorado Blood Cancer Institute, Denver, US. We asked, How can neurotoxicity associated with chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM) be managed?

In this interview, Dr Forsberg explored the evolving understanding and management of neurotoxicity associated with CAR T-cell therapy in MM. Forsberg highlighted current strategies for managing these toxicities and identifying patients at higher risk, and emphasized the importance of collaboration among healthcare professionals to refine diagnostic criteria and optimize therapeutic interventions as CAR T-cell therapies become integrated into the MM treatment paradigm.

Key learnings

• There are two CAR T-cell products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), currently approved for the treatment of MM.
• Both ide-cel and cilta-cel have been associated with immune effector cell-associated neurotoxicity syndrome (ICANS), a recognized complication of CAR T-cell therapy across indications including MM and lymphoma.¹
• The incidence of ICANS in myeloma is relatively low compared with other indications, and is generally considered to be manageable.
• The treatment of ICANS typically involves immunosuppressive therapy, primarily corticosteroids, but may require escalation in certain cases.²
• In addition to ICANS, cilta-cel has been associated with non-ICANS neurotoxicities, which are more variable in their timing and presentation compared with ICANS and may reflect different underlying mechanisms.²
  • Non-ICANS neurologic events include cranial nerve palsies, movement disorders, and neurocognitive changes.
  • Cranial nerve palsies are typically reversible and are managed using corticosteroids, intravenous immunoglobulin, and other supportive measures.
  • Movement disorders and cognitive changes tend to be less reversible and are more challenging to manage.
  • Treatment strategies for more complex non-ICANS events include investigational approaches such as cyclophosphamide or intrathecal methotrexate.
• Early identification of patients at risk for neurologic toxicity is a key focus in ongoing clinical research and practice.
• Substantial lymphocyte expansion following CAR T-cell infusion has emerged as a potential predictor of delayed neurologic events.
• At the Colorado Blood Cancer Institute, an exploratory approach has been developed in which dexamethasone is administered to patients with substantial lymphocyte expansion, as a potential preventive measure.³
  • This strategy is currently being implemented in a clinical setting and may offer benefit in reducing the incidence or severity of neurotoxicity.
  • Prospective studies are expected to evaluate the impact of this and other early intervention strategies.
• Ongoing collaboration across institutions is crucial to defining, managing, and preventing neurologic complications associated with CAR T-cell therapy.
• There is growing emphasis on moving from reactive treatment of neurotoxicity to proactive risk stratification and early intervention.
• As CAR T-cell therapy becomes increasingly integrated into the MM treatment paradigm, continued research and shared clinical experience are necessary to improve patient care.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.