Lenalidomide has multiple immunomodulatory effects that
provide antitumor properties and has been used in treatment of myeloma and AL
amyloidosis. Recently, several cases have been reported of acute allograft
rejection in patients who got this agent with a renal transplant.
Activation of the immune system by lenalidomide has been
shown to result in immune-mediated complications. In a retrospective analysis,
Montefusco et al discovered a 4-fold increased risk for the development of autoimmune disease following
the administration of lenalidomide for the treatment of multiple
myeloma, most of which occurred in the first 3 to 5 weeks after initiating
therapy.
Meyers et al had reported the first case of rejection in
a patient after heart-kidney transplantation with stable immunosuppression following
lenalidomide administration. Since then two additional cases are reported in
the renal transplant population both in the recent years.
The two cases are listed below
Transplantation Proceedings case report
Why does this happen? The authors of most articles
postulate that lenalidomide might activate T cells by directly inducing tyrosine
phosphorylation of CD28, an essential T-cell−signaling protein
in the costimulatory pathway. Direct activation of this pathway allows for T-cell
activation in the presence of CTLA4 immunoglobulin blockade,
increased secretion of interferon γ and IL-2, and stimulation of
cytotoxic CD8-positive and CD4-positive helper cells.
In addition to CTLA-4 antagonist and PD1 and PDL1
inhibitors that activate the immune system and cause transplant
rejection, we will have to add Lenalidomide to the list as well.
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