CAR-T Meeting 2024 | The detection and management of MNTs following BCMA-directed CAR-T therapy
Following BCMA-directed CAR T-cell therapy, movement and neurocognitive treatment-emergent adverse events (MNTs) may arise, and these adverse events differ from the neurotoxicity commonly observed with CAR-T administration. In this interview, Lukas Scheller, MD, University of Würzburg, Würzburg, Germany, discusses the risk factors for MNT, how patients should be monitored for MNT emergence, and how clinicians should manage this complication. This interview took place at the EBMT-EHA 6th European CAR T-cell Meeting in Valencia, Spain.
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Transcript (edited for clarity)
MNTs are movement and neurocognitive treatment-emergent adverse events. It’s a long word. And they first arose with the introduction of novel BCMA-directed CAR T-cells and they substantially differ from what we have seen neurotoxicity-wise for other CAR-T treatments before.
We currently know that high tumor burden, high-grade CRS, any grade ICANS, and also a high CAR T-cell expansion and persistence, are the major risk factors for these side effects, and some groups already identified that it’s most likely linked to BCMA expression in the patient’s basal ganglia...
MNTs are movement and neurocognitive treatment-emergent adverse events. It’s a long word. And they first arose with the introduction of novel BCMA-directed CAR T-cells and they substantially differ from what we have seen neurotoxicity-wise for other CAR-T treatments before.
We currently know that high tumor burden, high-grade CRS, any grade ICANS, and also a high CAR T-cell expansion and persistence, are the major risk factors for these side effects, and some groups already identified that it’s most likely linked to BCMA expression in the patient’s basal ganglia.
So, regarding the diagnostics, it is important to properly assess the patient for any neurological symptoms. But other than that, depending on the clinical situation, we may need to do spinal taps to check for other causes, but also for CAR-T infiltration, and also to take into account functional imaging of the brain.
For the treatment or management of MNTs, it is important to, first of all, probably interfere with the occurrence of CRS and ICANS by providing early and aggressively steroids and tocilizumab, and also to properly prepare the patient by debulking them to reduce the tumor burden prior to CAR-T. In the case of the occurrence of MNTs [with] coinciding excessive CAR-T expansion, it is also important to get rid of the CAR T-cells, most commonly by conventional chemotherapy like cyclophosphamide, but also intrathecal chemotherapy.
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