Cancer risk with alemtuzumab following kidney transplantation [feedly]

 
 

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Cancer risk with alemtuzumab following kidney transplantation

Abstract

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.

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Alemtuzumab Induction Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis

Alemtuzumab Induction Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis: Background: Alemtuzumab (MabCampath or Campath; Genzyme, Cambridge, MA) is a CD52-specific monoclonal antibody that causes profound and sustained lymphocyte depletion. Its use as an induction therapy in organ transplantation is increasing. Since our last systematic review in 2006, where we identified the need for good-quality randomized controlled trials (RCTs), several RCTs have been published that examine its efficacy and safety in kidney transplantation. The aim of this study was to evaluate the current evidence for alemtuzumab induction therapy in kidney transplantation.

Alemtuzumab Versus Interleukin-2 Receptor Antibodies Induction in Living Donor Kidney Transplantation

Alemtuzumab Versus Interleukin-2 Receptor Antibodies Induction in Living Donor Kidney Transplantation: Background. Alemtuzumab use has been increasing in kidney transplantation. We aimed to compare posttransplantation outcomes between alemtuzumab and interleukin-2 receptor antibodies (IL-2RA) in living donor kidney transplant recipients in the United States.
Methods. Organ Procurement Transplant Network/United Network of Organ Sharing data, as of August 2007, were used to identify all living donor kidney transplants performed in adults in the United States from 2003 to 2006 where induction therapy with alemtuzumab or IL-2RA (daclizumab or basiliximab) was used. Primary outcomes included incidence of acute rejection, graft survival, and patient survival.

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—An Open Label, Randomized Trial

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—An Open Label, Randomized Trial: Background. Immunosuppressive regimens for kidney transplantation which reduce the long-term burden of immunosuppression are attractive, but little data are available to judge the safety and efficacy of the different strategies used. We tested the hypothesis that the simple, cheap, regimen of alemtuzumab induction combined with tacrolimus monotherapy maintenance provided equivalent outcomes to the more commonly used combination of interleukin-2 receptor monoclonal antibody induction with tacrolimus and mycophenolate mofetil combination maintenance, both regimens using steroid withdrawal after 7 days.

Single shot of alemtuzumab as induction therapy after kidney transplantation is sufficient

Single shot of alemtuzumab as induction therapy after kidney transplantation is sufficient:

Summary

In an earlier study, we were able to show that Tac monotherapy following 2 × 20 mg alemtuzumab induction is at least as effective as Tac-based triple-drug immunosuppression in cadaveric renal transplantation. We were interested to learn whether 1 × 30 mg of alemtuzumab is as effective as 2 × 20 mg. Patients of the initial study group (group A) received 20 mg alemtuzumab on days 0 and 2, and tac monotherapy from day 2 on. This group acted as control group for the new arm (group C), where patients were given only 1 × 30 mg alemtuzumab on day 0 followed by Tac monotherapy from day 2 on with the same target levels as in the control group. Frequency of rejection at 6 months was 15% in the control group compared to 6% in the study group and 20% at 12 months in group A versus 6% in group C (P = 0.034). Time to rejection was 4.9 months in group A and 0.8 in group C. One-year patient survival was 98.5% in both groups, graft survival 96.9% in group A, and 98.5% in group C. Safety profile was similar in both groups apart from more viral and bacterial infections in group C. Single shot alemtuzumab induction of 30 mg is as effective as 2 × 20 mg in cadaveric renal transplantation.

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy-An Open Label, Randomized Trial

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy-An Open Label, Randomized Trial: Background. Immunosuppressive regimens for kidney transplantation which reduce the long-term burden of immunosuppression are attractive, but little data are available to judge the safety and efficacy of the different strategies used. We tested the hypothesis that the simple, cheap, regimen of alemtuzumab induction combined with tacrolimus monotherapy maintenance provided equivalent outcomes to the more commonly used combination of interleukin-2 receptor monoclonal antibody induction with tacrolimus and mycophenolate mofetil combination maintenance, both regimens using steroid withdrawal after 7 days.

Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome

Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome: "Background. Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied.
Methods. We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P=0.0016, 0.001, and 0.012, respectively).

Alemtuzumab Induction in Renal Transplantation

Alemtuzumab Induction in Renal Transplantation: (N Engl J Med 2011)

BACKGROUND

There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in renal-transplant recipients. The purpose of the present study was to compare induction therapy involving alemtuzumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk.

METHODS

In this prospective study, we randomly assigned patients to receive alemtuzumab or conventional induction therapy (basiliximab or rabbit antithymocyte globulin). Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 20% or more, or black race. The 139 high-risk patients received alemtuzumab (one dose of 30 mg, in 70 patients) or rabbit antithymocyte globulin (a total of 6 mg per kilogram of body weight given over 4 days, in 69 patients). The 335 low-risk patients received alemtuzumab (one dose of 30 mg, in 164 patients) or basiliximab (a total of 40 mg over 4 days, in 171 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 5-day glucocorticoid taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 3 years for safety and efficacy end points.