Neurologic adverse events manageable after CAR-T in multiple myeloma
Neurologic adverse events were generally manageable in patients with multiple myeloma after receiving ciltacabtagene autoleucel, a BCMA-directed CAR T-cell therapy, according to CARTITUDE-2 data presented at the virtual ASCO Annual Meeting.
“Treatment-emerging neurotoxicities are known side effects of CAR-T cell therapies,” Hermann Einsele, MD, from the University Hospital of Würzburg in Germany, said in the presentation. “Here we present patient management strategies to identify and reduce the incidence of neurological adverse events in CARTITUDE-2.”
Researchers enrolled lenalidomide-refractory patients with progressive multiple myeloma after 1 to 3 prior lines of treatment (including PI and IMiD) in cohort A of this ongoing, phase 2 study. Patients underwent apheresis then bridging therapy as needed followed by lymphodepleting therapy with cyclophosphamide and fludarabine. On day 1, patients received ciltacabtagene autoleucel (cilta-cel; Janssen, Legend Biotech) at a target dose of 0.75 million cells per kilogram body weight, according to the presentation.
Monitoring and mitigation strategies for neurologic adverse events included bridging therapy to reduce baseline tumor burden, frequent assessment and early aggressive treatment of CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) and handwriting assessments to detect neurotoxicity symptoms. Management strategies included examining infectious and paraneoplastic etiologies, administering tocilizumab and/or dexamethasone or methylprednisolone when necessary.
Of the 20 patients treated with cilta-cel in cohort A evaluated as of January 15, 2021, (median follow-up, 5.8 months), neurotoxicities occurred in four patients (20%). Overall, three patients developed grade 1 or 2 ICANS; median time to ICANS symptom onset was 8 days and median duration was 2 days. Two of these patients received supportive measures to treat ICANS (including levetiracetam and steroids); all three patients had concurrent grade 1 or 2 CRS, and all recovered. Researchers observed no movement or neurocognitive disorders.
In addition, one patient developed isolated facial paralysis on day 29 after cilta-cel infusion, which was successfully treated with dexamethasone for 1 month and the patient recovered 51 days after onset. In his presentation, Einsele said that none of the patients in this CARTITUDE-2 cohort A study experienced other neurotoxicities that were seen in CARTITUDE-1.
“The implementation of patient management strategies appeared to reduce the risk of movement and neurocognitive treatment-associated [adverse events],” Einsele said. “Early detection and management of neurological adverse events can help to optimize patient care after CAR-T therapy. When implemented, patient management strategies have reduced the incidence of neurotoxicity including movement and neurocognitive adverse events.”
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Einsele H, et al. Abstract 8028. Presented at: ASCO Annual Meeting; June 4-8, 2021 (virtual meeting).
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