Alemtuzumab-Based Induction Promising for Kidney Transplant

By David Douglas

August 15, 2014

NEW YORK (Reuters Health) - Compared to standard basiliximab-based induction therapy, treatment based on alemtuzumab reduces rejection in kidney transplant recipients, according to findings from a UK-based study.

As Dr. Peter Friend told Reuters Health by email, the trial "has demonstrated that a very short course of treatment (2 injections) shortly after transplantation has a major effect on the risk of rejection of the transplant (58% reduction) and that it achieves this in the context of reduced levels of long-term maintenance immunosuppressive drugs."

In a paper online July 28 in The Lancet, Dr. Friend of the University of Oxford and colleagues note that calcineurin inhibitors reduce short-term kidney transplant failure, but might contribute to transplant failure in the long-term.

Using alemtuzumab, a potent lymphocyte-depleting antibody, could allow early reduction in calcineurin inhibitors and mycophenolate exposure as well as steroid avoidance, they add.

The team randomized 426 patients to alemtuzumab-based treatment (alemtuzumab followed by low-dose tacrolimus and mycophenolate without steroids) and 426 patients to basiliximab-based treatment (basiliximab followed by standard-dose tacrolimus, mycophenolate, and prednisolone).

At six months' follow-up, 31 patients in the alemtuzumab group and 68 patients in the basiliximab group showed biopsy-proven acute rejection (hazard ratio, 0.42; p<0.0001).

"Importantly," stressed Dr. Friend, this improvement "was not achieved at the cost of increased complications, particularly serious infection."

The implications, he added, "go beyond the reduction of transplant rejection. The ability to modify maintenance immunosuppression may have real benefits with respect to the long-term survival of transplants (chronic toxicity of commonly-used drugs is thought to be a major factor in the steady attrition of transplanted kidneys)."

"Proving this hypothesis, however," Dr. Friend concluded, "will require the longer-term follow-up of this trial."

Dr. Dirk Kuypers, who wrote an editorial on the findings, told Reuters Health that the researchers "have clearly demonstrated that alemtuzumab induction therapy combined with tacrolimus and mycophenolate mofetil but without corticosteroids, can safely achieve short-term efficacy results comparable to the current standard of care immunosuppressive therapy in kidney transplantation."

"The biggest challenge is to demonstrate that alemtuzumab induction therapy will allow for the safe maintenance of a calcineurin-inhibitor-free treatment with improved long-term graft outcomes and a better side effect profile for the patients," Dr. Kuypers, of the University of Leuven in Belgium, told Reuters Health by email.

The study was partly funded by Pfizer and Novartis UK.

SOURCE: http://bit.ly/1yzTbDF and http://bit.ly/1sY2ZFZ

Lancet 2014.

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