Alemtuzumab in Lung Transplantation: An Open-Label, Randomized, Prospective Single Center Study

Abstract

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ! A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p ¼ 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

Alemtuzumab Induction in Lung Transplantation: Time to Move On?

“…The trial results of Jaksch et al (2), are in keeping with the broader experience with alemtuzumab induction in recipients of other solid organs. While these prior randomized trials (4) consistently demonstrated decreased early acute rejection events in patients receiving alemtuzumab induction, there were no comparable differences in long-term allograft or patient survival.…”

“…In summary, the study reported by Jaksch et al (2) demonstrates alemtuzumab induction is not a game changer for the lung transplant community and reminds us that more effective strategies to promote tolerance will be needed in order to improve allograft survival and limit unwelcome toxicities. In essence, we are still using an axe when we need the precision of a scalpel to directly target detrimental cell populations or signaling pathways, while maintaining those that promote tolerance or protective immunity.…”

“…Given the paucity of rigorous clinical trials addressing induction strategies for lung transplantation, the current study by Jaksch et al (2) is a welcome addition to the literature.…”

“…To this point, Krupnick et al (8) recently reported on the essential role for CD8 þ central memory T cells in promoting experimental lung allograft tolerance, underscoring the idea that eliminating CD8 cells at the time of transplantation is not without consequence. We remain optimistic that further progress in the field will be achieved as innovative agents are developed and the lung transplant community continues to embrace high quality study designs, as was employed by Jaksch et al (2), to define best clinical practices.…”

Montelukast for Bronchiolitis Obliterans Syndrome After Lung Transplantation: A Randomized Controlled Trial

“…Other treatment options, such as total lymphoid irradiation (TLI) [11][12][13] and extracorporeal photopheresis (ECP) [14] proved to be of some benefit in the treatment of patients with BOS. Some positive effects of alemtuzumab (anti-CD52) in CLAD have also been reported [15].…”