What is the role of alemtuzumab (Campath-1H) in immunosuppression after solid organ transplantation?

Updated: Jan 04, 2016
  • Author: Bethany Pellegrino, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Humanized monoclonal anti-CD52 antibody (alemtuzumab)

Alemtuzumab (Campath-1H), a humanized monoclonal antibody directed against CD52, is a lymphocyte-depleting agent currently being evaluated as an induction agent in solid organ transplantation. Alemtuzumab has been used in off-label studies of solid organ transplantation. CD52, a 25- to 29-kd membrane protein and is on all B and T cells and most macrophages and natural killer cells. Alemtuzumab has powerful depletional properties and a favorable cost profile compared with other induction agents. Treatment results are a rapid and effective depletion of lymphoid cells that may take several months to return to pretransplantation levels.

Alemtuzumab induction and tacrolimus monotherapy was analyzed in 42 pediatric consecutive living-donor kidney transplantations. No patients had antibody-mediated rejection. Tacrolimus monotherapy was attempted in 16 (38%) and was successful in 12 (26%) patients. All patients were steroid free. There was no tissue invasive CMV disease or infection, no BK/polyoma viral nephropathy, and no posttransplantation proliferative disease. This study revealed the 4-year safety and efficacy of this approach in pediatric recipients.

Alemtuzumab induction was found to be safe in deceased donor kidney transplantation, with satisfactory patient and graft survivals at 1 year. Alemtuzumab induction was found to be safe even for recipients of extended criteria donor renal transplantation. Serious adverse events were absent; there was no hyperlipidemia or new-onset diabetes. There was no acute rejection. The 3 (27%) recipients with infectious complications experienced pericardial tuberculosis, urinary tract infection, or invasive pulmonary aspergillosis. Two (18%) cases of posttransplantation lymphoproliferative disease were diagnosed in this study during the follow-up. Overall, patient and graft survival rates were both 91%.

Alemtuzumab induction and tacrolimus monotherapy in 200 living donor solitary kidney transplantations with 3 years of follow-up revealed the actuarial 1-, 2-, and 3-year patient and graft survivals were 99%, 98%, 96.4% and 90.8%, 93.3%, 86.3%, respectively. Fifty (25%) recipients had a total of 89 episodes of acute cellular rejection. About 88.7% of acute cellular rejection episodes were Banff 1, and of those, 82% were steroid sensitive. Nine (4.5%) recipients had antibody-mediated rejection. About 76.5% were weaned but only 46% are currently on spaced-dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroid-free from the time of transplantation. Infectious complications were uncommon.

National registry data indicate a trend towards the incorporation of lymphocyte-depletion antibody-induction therapy into immunosuppressive regimens for solid organ transplantation. In general, alemtuzumab is well tolerated and substantially reduces the risk of acute rejection in the first 6 months posttransplantation in nonsensitized recipients. There is little evidence to support the notion that it uniquely promotes tolerance, and growing evidence suggests it is ineffective in the setting of allosensitization. Alemtuzumab-treated patients clearly remain dependent on maintenance immunosuppression. Long-term outcome data are required to determine the magnitude and type of maintenance therapy that makes best use of alemtuzumab's depletional effects.

The use of alemtuzumab as induction immunosuppression for renal transplantation introduces the possibility of long-term tacrolimus monotherapy, avoiding maintenance with both corticosteroids and mycophenolate mofetil. Renal transplantation with alemtuzumab induction followed by tacrolimus monotherapy leads to good graft and patient outcomes, with no major differences detected compared with basiliximab induction and tacrolimus/mycophenolate mofetil maintenance at 1 year. It was shown that alemtuzumab induction is associated with delayed inflammation at 4 and 12 months, but this inflammation did not appear to negatively impact the glomerular filtration rate or graft survival.

Adverse effects of alemtuzumab include mild cytokine-release syndrome, neutropenia, anemia, idiosyncratic pancytopenia, autoimmune disorders (eg, hemolytic anemia), thrombocytopenia, and thyroid disease. Further controlled trials are needed to establish safety and efficacy. The risk of immunodeficiency-related malignancies was evaluated in a retrospective study including 1350 kidney transplant recipients (between 2001 and 2009). The study concluded that with the exception of nonmelanoma skin cancer and after excluding cancers occurring within 60 days posttransplantation, alemtuzumab induction was not associated with increased cancer incidence post kidney transplantation when compared with no induction therapy and was associated with lower cancer incidence compared with thymoglobulin.


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