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EBMT 2025 | The risk of myelopathy following CAR-T and managing this rare complication
Parastoo Dahi, MD, MS, Memorial Sloan Kettering, New York City, NY, comments on the risk of acute myelopathy following CAR T-cell therapy, a rare but serious complication that requires prompt identification and intervention. Dr Dahi highlights that, in an analysis of published case reports, all cases of myelopathy occurred in patients who experienced cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) prior to the onset of myelopathy. Dr Dahi also provides insight into the management of patients with this complication. This interview took place at the 51st Annual Meeting of the EBMT in Florence, Italy.
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Transcript
Myelopathy is rare, but a very serious neurologic complication that can occur after CAR T-cell therapy and can lead to significant morbidity and requires prompt identification and intervention. It is rare. When we looked at the published case reports, there were 24 cases in total that were reported, of myelopathy – 20 in adult patients and four pediatric patients with lymphoma or lymphoblastic leukemia that had received CD19 or CD22 targeted CAR T-cell therapy...
Myelopathy is rare, but a very serious neurologic complication that can occur after CAR T-cell therapy and can lead to significant morbidity and requires prompt identification and intervention. It is rare. When we looked at the published case reports, there were 24 cases in total that were reported, of myelopathy – 20 in adult patients and four pediatric patients with lymphoma or lymphoblastic leukemia that had received CD19 or CD22 targeted CAR T-cell therapy.
And, you know, these patients, most of the CAR-T product in these patients contained the CD28 costimulatory domain, which is known for a higher inflammatory response, higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and all of the cases had experienced CRS and ICANS prior to the onset of myelopathy.
And they presented with different symptoms, paraplegia, quadriparesis, loss of sensation, bladder dysfunction, and so forth. And the management basically varied, but it included high doses of steroids. In some cases, intravenous immunoglobulin (IVIG), plasmapheresis, or tocilizumab, siltuximab, and anakinra. Of these 24 cases that have been reported, six of them died, but of those who survived, almost all of them remained in remission at the last time of follow-up, suggesting that the high doses of steroids that they had received for myelopathy did not compromise the efficacy of the CAR T-cells.
And you’re questioning about management. So I think early diagnosis and intervention is key. So as soon as, you know, there are new or worsening neurologic symptoms, the recommendation is to do a prompt imaging evaluation with MRI of the brain and the spine. Get neurologists and the infectious disease specialists involved. If feasible, proceed with a lumbar puncture and cerebrospinal fluid (CSF) analysis. And this is not only to evaluate the opening pressure and for CSF diversion potentially, but also to, but also to look into other etiologies that could be there, such as infectious causes. And the main treatment for myelopathy is high doses of steroids. Now, other supportive measures have been reported and seem to be also a valuable intervention, such as IVIg or rehabilitation, physical therapy, occupational therapy, and in some cases, surgical interventions for CSF diversion.
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