Clinical Scorecard: CAR T cells may improve walking in stiff person syndrome

At a Glance

Key Highlights

• In the 26 treated patients, median timed 25-foot walk time decreased 45.6% at week 16; 21 patients (80.8%) improved by at least 20%.
• Among 12 patients who used a walking aid at baseline, 8 no longer needed assistance at week 16.
• Secondary measures of disability, stiffness, sensory sensitivity, and ambulation improved; 25 patients (96.2%) improved on at least one primary or secondary efficacy measure.
• Treatment-related adverse events occurred in all patients. Cytokine release syndrome occurred in 24 (92.3%), and immune effector cell–associated neurotoxicity syndrome occurred in 3 (11.5%); all cases were grade 1 or 2 and resolved without sequelae.
• The small, uncontrolled trial and short follow-up limit conclusions about comparative efficacy and durability; only 16 patients had reached the week-24 assessment.

Guideline-Based Recommendations

Diagnosis

• Trial eligibility required antibody-positive SPS and an inadequate response to at least one immunomodulatory treatment.

Management

• The study protocol required discontinuation of immunomodulatory or immunosuppressive therapy before infusion; all treated patients remained off these therapies during follow-up.
• The trial regimen included 3 days of lymphodepleting fludarabine and cyclophosphamide followed by a single intravenous infusion of 100 million autologous CD19-directed CAR T cells.
• The study authors identified access to physicians experienced in CAR T-cell therapy and management of potential associated events as a practical consideration.

Monitoring & Follow-up

• The primary efficacy endpoint was change from baseline to week 16 in the timed 25-foot walk test; secondary measures included the modified Rankin Scale, Distribution of Stiffness Index, Heightened Sensitivity Scale, and Hauser Ambulation Index.
• Safety assessment included monitoring for cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and cytopenias.
• Long-term follow-up is in progress; the study reported a median follow-up of 6.5 months.

Risks

• Cytokine release syndrome occurred in 24 of 26 patients (92.3%); all cases were grade 1 or 2. Tocilizumab and corticosteroids were each used in 21 patients.
• Immune effector cell–associated neurotoxicity syndrome occurred in 3 patients (11.5%); all cases were grade 1 and resolved without sequelae.
• Grade 3 or 4 neutropenia occurred in 5 patients (19.2%); 11 patients (42.3%) had at least one grade 3 or higher treatment-related adverse event.
• Three patients (11.5%) experienced treatment-related serious adverse events. No deaths or adverse-event-related treatment discontinuations were reported.

Patient & Prescribing Data

Twenty-seven patients were enrolled and 26 treated. Eligible patients were aged 18 to 75 years, had antibody-positive SPS, and had an inadequate response to at least one immunomodulatory treatment. Median age was 56 years; 16 (61.5%) were female.

Patients received lymphodepleting fludarabine and cyclophosphamide for 3 days, followed by one intravenous infusion of 100 million autologous CD19-directed CAR T cells. All treated patients had discontinued immunomodulatory or immunosuppressive therapy before infusion and remained off these treatments during follow-up.

Clinical Best Practices

• Interpret the reported mobility and secondary-scale improvements in light of the trial's small size, nonrandomized design, lack of a control group, and short follow-up.
• Do not infer comparative efficacy or long-term durability from these results; the authors reported that long-term follow-up is ongoing.
• Consider the study population when applying findings: results may not generalize to patients with less severe or antibody-negative SPS.
• Account for the need for clinicians experienced in CAR T-cell therapy and management of potential associated events, as noted by the study authors.

Related Resources & Content

• JAMA Neurology; KYSA-8 phase 2 trial report (citation details and URL not provided in source)