Case Study Shows Efficacy of BCMA-CD19 Bispecific CAR-T Therapy in Refractory CIDP

A case study of a 44-year-old man published in hLife demonstrated the efficacy of BCMA-CD19 bispecific CAR-T cells for the treatment of refractory chronic inflammatory demyelinating polyneuropathy (CIDP). Although this was a single case study, the results suggest that a larger sample size and long-term follow-up studies assessing this therapeutic may provide clinical value for patients with CIDP and other neurological diseases.¹

After CAR-T cell therapy administration, the man reported a temporary exacerbation of weakness and numbness as well as myalgia in both lower limbs. Following this transient worsening, the patient's status markedly improved on Inflammatory Neuropathy Cause and Treatment (INCAT) disability and Medical Research Council (MRC) sum scores. The patients’ muscle strength recovered almost completely on day 180 following CAR-T cell initiation.

The study featured a man with CIDP who presented with recurrent episodes of numbness and weakness in the distal extremities. Following an admission assessment and discussion on treatment options, the patient started CAR-T therapy. Conducted by senior author Jun-Nian Zheng, MD, PhD, director of Institute of Cancer Biotherapy at Xuzhou Medical University in China, and colleagues, the treatment protocol and management of CAR-T cells were administered as previously done in research.² The primary end point was safety and secondary end points were CAR-T cell levels in the blood and ability of serum antibodies clearance. Additionally, the key exploratory outcome was efficacy which was measured by INCAT sensory, INCAT, and MRC scores.

Top Clinical Takeaways

The BCMA-CD19 bispecific CAR-T cell therapy demonstrated potential efficacy in a patient with refractory CIDP, with marked improvement in neurological function.
The therapy was associated with transient side effects, including fever, mild cytokine release syndrome, and hypotension, but these were managed effectively.
Long-term follow-up and larger studies are necessary to fully evaluate the therapeutic potential and safety of CAR-T cell therapy for CIDP and other neurological conditions.

Following infusion of 1 × 106 CAR-T cells per kilogram of body weight, CAR-T cells underwent 2 rounds of in vivo expansion. Authors noted that the activation of CAR-T cells by B cells in peripheral blood possibly prompted the initial expansion of CAR-T cells in vivo. Then, investigators reported that the cells in the spleen and bone marrow likely mediated the reamplification of CAR-T cells. In the study, CD19+ B cells deleted to 0 from day 10 following the CAR-T cell infusion and started to return 3 months afterward. Moreover, white blood cells slowly returned to normal in the third month following infusion. The levels of immunoglobulin dropped to the lowest in the blood on day 90 after infusion and then increased later on.

At baseline, the patient completed a 10m walk at 21s, which shortened to 13s on day 180 after CAR-T cell therapy. Authors also observed significant improvements in electrophysiological measurements of the median, ulnar, common peroneal, and tibial nerves following treatment. After 180 days of observation, investigators performed a follow-up every 90 days with the patient to assess if there was any recurrence or worsening of the disease. Authors highlighted that at 1 year, all immunosuppressive agents could successfully be discontinued without signs of disease relapse, and the patient’s sustained anti-GM4 and anti-GD3 antibodies disappeared following 3 months of CAR T-cell treatment.

In terms of safety, the patient had a fever and transient IL-6 elevation 6 to 14 days following CAR-T cell therapy which was managed symptomatically with acetaminophen. Authors noted that grade 1 mild cytokine release syndrome resolved in 2 weeks in the patient. Notably, after the CAR-T-cell transfer, the patient reported 2 episodes of fever which researchers noted might have been associated with the 2 rounds of CAR-T-cell expansion in vivo. Furthermore, the patient developed hypotension 1 to 15 days following CAR-T cell infusion, which he recovered from after 2 weeks of bed rest and drinking lots of fluids. Investigators observed no other toxicities related to CAR-T cell therapy in this study.