Alemtuzumab Increases CMV Infection Risk

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Bettina Knoll, MD, PhD
Bettina Knoll, MD, PhD

VANCOUVER, British Columbia—Cytomegalovirus (CMV) infection in kidney or kidney/pancreas transplant recipients occurs more frequently when alemtuzumab is used for induction instead of antithymocyte globulin (ATG), according to a new study from the University of Minnesota.

In addition, in alemtuzumab recipients, investigators observed more organ-invasive CMV disease in patients who received more than three doses of the agent.

Alemtuzumab (Campath-1H, MabCampath) is a humanized monoclonal CD52 antibody that, when administered, leads to rapid long-lasting lymphocyte depletion. B-cells return in two to 12 months, but the number of circulating T lymphocytes (particularly CD4 T cells) can remain depressed for years.

Today, alemtuzumab is used in steroid avoidance and calcineurin inhibitor minimization protocols in solid organ transplantation. Studies have shown that this agent is effective for induction and treatment of rejection. It has been theorized that alemtuzumab-induced long-term lymphocyte depletion may predispose a patient to an increased rate and severity of infections. However, studies to substantiate this theory in solid organ transplant recipients have come to discordant results.

“A high suspicion for CMV infection has to be maintained for patients who receive alemtuzumab therapy, and as observed in our study, patients can develop CMV [infection] despite being on prophylaxis with valganciclovir,” said study investigator Bettina Knoll, MD, PhD, a transplant infectious disease fellow at Massachusetts General Hospital, Boston. She presented study findings at the 48th Annual Meeting of the Infectious Diseases Society of America.

The study included recipients of kidney, pancreas, and combined kidney/pancreas transplants from February 2003 to April 2004. Patients had at least five years of follow-up. The investigators divided subjects into three groups: group 1 (33 patients) received three or fewer doses of alemtuzumab, group 2 (72 patients) received more than three doses of alemtuzumab, and group 3 (106 patients) received alemtuzumab-free ATG induction.

The mean number of alemtuzumab doses in groups 1 and 2 was 2.3 and 8.0, respectively. In group 3, 65% of patients were solitary kidney recipients compared with 21% in group 1 and 4% in group 2. The mean time of CMV prophylaxis with valganciclovir was 10.7 months post transplant for group 1, and 17.3 months for group 2. The mean time of CMV prophylaxis for group 3 was 4.9 months. The mean time of CMV prophylaxis after the last dose of alemtuzumab was 9.5 in group 1 and 2.

Mean CMV-free survival post-transplant was 20.4 months in group 3, which was significantly

longer when compared with 8.2 months in group 1 and 10.2 months in group 2.The mean time to first CMV infection (CMV syndrome or disease) after the last alemtuzumab dose was 9.9 months in group 1 and 5.3 months in group 2. In addition, the number of CMV infection episodes was nine in group 1, 32 in group 2, and 16 in group 3. More organ-invasive disease was observed in group 2:  CMV colitis developed in three patients, CMV pancreatitis developed in one patient, and CMV retinitis developed in two patients. In group 1, organ-invasive disease (colitis) was only observed in one patient.

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