Abstract: TH-PO1160
Alemtuzumab for Relapsing and Refractory Primary Systemic Vasculitis: A Trial of Efficacy and Safety (ALEVIATE)
Session Information
- Late-Breaking Clinical Trials Posters
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Gopaluni, Seerapani, University of Cambridge, Cambridge, United Kingdom
- Smith, Rona M., Cambridge University Hospitals, Cambridge, United Kingdom
- Goymer, Donna, Cambridge University Trust Foundation Hospitals, Cambridge, United Kingdom
- Broadhurst, Elizabeth, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
- Mcclure, Mark E., University of Cambridge, Cambridge, United Kingdom
- Cahill, Hugh Christopher, Cambridge University Hospitals, Cambridge, United Kingdom
- Jayne, David R.W., University of Cambridge, Cambridge, United Kingdom
Background
Primary systemic vasculitis encompassing ANCA associated vasculitis (AAV) and Behcet’s Disease (BD) has considerable morbidity & mortality. Inadequate response and relapses are common. There is an unmet need for safer therapy that leads to sustained remission in patients with relapsing or refractory disease (RD). Alemtuzumab(ALZ), an anti-CD52 mAb depletes lymphocytes for prolonged periods and was shown in observational studies to induce remission in RD. This trial’s aim is to determine the efficacy and safety of ALZ in patients with RD.
Methods
Randomized, prospective, open label, dose ranging clinical trial. 24 patients with RD randomized to receive either 60mg or 30mg of ALZ. Eligible patients were required to have failed to respond to standard therapies (cyclophosphamide/rituximab in AAV or anti-TNF therapy in BD). Patients > 60 yrs, creatinine >150umol/L, requiring intensive care unit support were excluded. Treatment was repeated at 6 months(M) or earlier where clinically appropriate. Each patient was followed up for 12M or until withdrawal. Co-trimoxazole and acyclovir prophylaxis was administered. Primary end-points: Proportion of patients with treatment response at 6M(Complete remission-CR: BVAS/WG of 0 for > 1M. Partial remission-PR: No severe BVAS/WG items and >=50% fall in BVAS/WG from entry) & proportion with a severe adverse event(SAE; CTCAE grade >=3).
Results
Evaluable patients:23. Mean age 36.8(10.9) yrs; M:F=9:15; AAV:12; BD:11; withdrawals:6/23(26%)-all due to progressive disease. Response(CR/PR) at 6M:15/23(65.2%; 95%CI: 0.43-0.84); 5/23(22%; 95%CI: 0.08-0.44) had remission that lasted to 12M. 10/15 (66.6%, 95% CI: 0.38-0.88) achieving remission had a relapse during the follow-up period. Of the 8 SAEs in 6 patients(26%), 5 were treatment related (1 CMV colitis, 1 viral gastroenteritis, 1 c.difficile infection; 2 infusion related reactions) and the other 3 were due to relapse. Small sample size precluded dose comparison analysis.
Conclusion
In this small phase II RCT testing the efficacy and safety of ALZ to treat RD, 65% of the patients achieved clinical remission at 6M. Even though relapses were common, 22% achieved sustained remission. SAEs were seen in 26% of the patients. This study indicates that ALZ is a safe therapy in a select group of patients.
Funding
- Commercial Support – Genentech