CIDP Development Following Cilta-cel Therapy in Relapsed Multiple Myeloma
Overview
Two female patients with relapsed multiple myeloma developed chronic inflammatory demyelinating polyneuropathy (CIDP) after receiving BCMA-targeted CAR-T cell therapy (cilta-cel). Both exhibited neurological symptoms weeks post-infusion, with partial response to immunosuppressive treatments and differing clinical outcomes.
Background
Ciltacabtagene-autoleucel (cilta-cel) is a BCMA-directed CAR-T cell therapy approved for relapsed/refractory multiple myeloma. While effective, CAR-T therapies can cause severe adverse events including neurological complications, typically early post-infusion. CIDP is a rare immune-mediated demyelinating disorder of peripheral nerves, and its occurrence following BCMA CAR-T therapy is not well characterized. This report describes two cases of CIDP developing after cilta-cel treatment, highlighting clinical features, immunopathology, and treatment responses.
Progressive neurological decline, death at 114 days post symptom onset
Gradual neurological improvement, discharged 86 days post symptom onset
Infectious complications
Recurrent pneumonia, invasive aspergillosis
COVID-19 pneumonia, urosepsis
Key Findings
Both patients developed CIDP with mixed sensorimotor axonal demyelinating polyneuropathy weeks after cilta-cel infusion.
CAR-T cells were detected in peripheral blood and CSF; patient 2 also had CAR-T cells in bone marrow.
Standard CIDP treatments (high-dose dexamethasone and IVIG) provided partial symptom control; cyclophosphamide was added due to progressive neurological decline.
Patient 2 showed neurological improvement correlating with decreased CAR-T cell levels; patient 1 had persistent CAR-T cells and progressive deterioration.
Serious infectious complications occurred in both patients, requiring intensive care admission.
Immunophenotyping revealed expansion of CD8+ non-CAR-T effector and memory T cells, with minimal CAR-T cell proportion among T cells.
Clinical Implications
Clinicians should be aware of the potential for delayed-onset CIDP following BCMA-directed CAR-T therapy, even in the absence of early neurotoxicity. Early recognition and aggressive immunosuppressive treatment including corticosteroids, IVIG, and cyclophosphamide may improve neurological outcomes. Monitoring CAR-T cell kinetics and immune cell subsets could guide therapeutic decisions and prognosis.
Conclusion
CIDP can develop as a rare, delayed neurological complication after cilta-cel therapy for multiple myeloma. Multimodal immunosuppressive therapy may partially control symptoms, but outcomes vary, underscoring the need for vigilance and further research into pathogenesis and management.
References
Author/Source/Year -- Development of chronic inflammatory demyelinating polyneuropathy (CIDP) following cilta-cel treatment
by M. Korenkov, J. Liebaert, S. Yousefian, S. Schwartz, U. M. Demel, J. Braune, M. C. Odabasi, L. Herzberg, D. Böckle, N. C. Görür, V. v. Landenberg-Roberg, S. Bohl, E. Tregel, S. Hennig, C. Franke, S. Haas, U. Keller, J. Krönke, A. Busse
The tool, called PANGEA-SMM, outperforms existing predictive tools by more accurately determining when smoldering multiple myeloma is progressing and requires treatment. The free online tool can be used immediately to monitor patients.
