Mitigation strategies based on prior reports of immune effector cell-associated neurotoxicity syndrome (ICANS) after treatment with ciltacabtagene autoleucel (cilta-cel) reduced the incidence of movement and neurocognitive treatment-emergent adverse events (MNTs) in patients with multiple myeloma (MM). These findings were published in Blood Cancer Journal.

Data for this study were sourced from CARTITUDE-1, a phase 1b/2 trial of the chimeric antigen receptor (CAR) T-cell therapy cilta-cel. In this trial of 97 patients with MM, 5 (5.2%) patients experienced MNTs following treatment with cilta-cel. The events were experienced a median of 27.0 days (range, 14 to 108) after treatment initiation.

The patients who experienced MNTs were evaluated for common features, and potential MNT mitigation strategies were formulated.


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The risk of MNT was associated with high cell expansion (odds ratio [OR], 48.6), ICANS (OR, 26.7), high baseline tumor burden (OR, 9.1), day 28 absolute lymphocyte count (ALC; OR, 3.4), day 21 ALC (OR, 2.3), day 14 ALC (OR, 1.5), and baseline interleukin-6 (OR, 1.2).

Using these trends, preventive, monitoring, and management strategies were formulated. Preventive strategies included enhanced bridging therapy and risk-benefit discussions with patients at risk for significant disease burden. Monitoring strategies included handwriting assessments with a tool for early detection of neurotoxicities and monitoring and reporting time extended to up to 1 year after CAR T-cell therapy.

Management strategies included earlier, more aggressive supportive care and use of tocilizumab for any grade ICANS and/or dexamethasone (grade 1-3) or methylprednisolone (grade 4), cytokine-targeting therapies, and consideration of prophylactic nonsedating antiseizure medications for grade 2 or higher neurotoxicity.

In the CARTITUDE-2 study, the incidence of MNTs after implementing mitigation strategies was significantly lower. More than 150 patients received cilta-cel, and only 1 reported an MNT.

The limitation of this study was the low rate of MNTs overall, so all risk factors may not have been accounted for.

These data indicated that early mitigation strategies successfully decreased the rate of MNTs after CAR T-cell therapy in patients with MM.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Cohen AD, Parekh S, Santomasso BD, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 2022;12(2):32. doi:10.1038/s41408-022-00629-1

This article originally appeared on Oncology Nurse Advisor