Christoph Groth, University Hospital of Muenster, Muenster, Germany, and colleagues conducted a phase I/II trial to evaluate the safety and efficacy of an immunotoxin-combination, a mixture of anti-CD3 and anti-CD7 antibodies separately conjugated to recombinant ricin A (CD3/CD7-IT) for the treatment of patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD). This immunotoxin-combination causes in-vivo depletion of T- and NK-cells and regulates T-cell receptor activation. The findings of this study were publishedahead of print in the Biology of Blood and Marrow Transplantation .
Patients received 4 mg/m 2CD3/CD7-IT in four 4-hour intravenous infusions administered at 48-hour intermissions. GvHD prophylaxis included cyclosporine-A alone or in combination with mycophenolate mofetil. Prophylaxis was continuously administered during treatment with CD3/CD7-IT.
- N = 20 patients with SR-aGvHD, 85% of these had severe SR-aGvHD
- Median age: 53 years (range, 18–74)
- All patients had visceral organ involvement:
- N = 18 gastrointestinal (GI)
- N = 5 liver (25%) involvement
- Median follow-up: 292 days (range, 3–889)
- Two patients died of disease progression before completing treatment
- N = 18 patients (90%) received all four scheduled doses of therapy
- Overall response rate: 60% (95% CI, 36–81%)
- Complete response rate: 50% (95% CI, 27–73%)
- 6-month overall survival rate: 60% (95% CI, 36–78%)
- Eight patients died on trial due to refractory aGvHD (4 patients), refractory GvHD with infection (3 patients), and pseudomembranous colitis (1 patient)
- Treatment-related AEs included hypoalbuminemia, microangiopathy, and thrombocytopenia
- One-week treatment course led to T- and NK-cell depletion with rapid recovery of the immune system
This study indicates that CD3/CD7-IT is safe with “relatively low prevalence of manageable and reversible adverse events, primarily worsening of hypoalbuminemia, microangiopathy, and thrombocytopenia” for SR-aGvHD patients. Furthermore, this data suggests that CD3/CD7-IT is a promising treatment option for patients with SR-aGvHD.