Orthotopic heart transplant rejection in association with immunomodulatory therapy for AL amyloidosis: A case series and review of the literature

Abstract

Although end‐organ damage caused by AL amyloidosis historically portends a poor prognosis, advances in therapy in combination with solid organ transplantation can lead to significant improvements in survival. Immunomodulatory agents (IMiDs), such as lenalidomide and pomalidomide, are an effective class of drugs in the treatment of AL amyloidosis. However, there is growing concern that these agents may precipitate acute transplant rejection via upregulation of interleukin‐2 and inhibition of immune tolerance. This case series describes three patients who underwent orthotopic heart transplantation for AL amyloidosis and later had progression of their underlying plasma cell dyscrasia, leading to treatment with IMiD therapy. Two patients subsequently developed acute allograft rejection, including the first reported case of pomalidomide‐associated allograft rejection. The third patient tolerated long‐term therapy without signs of rejection: the first reported case of IMiD tolerability after heart transplant. These cases, together with a review of the literature, demonstrate variable outcomes and elucidate the potential risk of organ rejection associated with the use of IMiDs. When treatment with IMiDs is necessary, close surveillance and modification of immunosuppression may mitigate risks of rejection and complications.

Current Updates on the Management of AL Amyloidosis

“…However, it is not clear if this increase is related to the direct cardiotoxic effect of IMiDs or fluid retention, causing an elevation in NT-proBNP [ 96 ]. Additionally, as IMiDs can upregulate parts of the immune system, they should not be used in patients after solid organ transplantation due to the risk of precipitating acute rejection [ 97 ].…”

Cardiac Transplantation and Mechanical Circulatory Support in Amyloidosis

“…Indeed, the proteasome inhibitor bortezomib has been used in both the treatment of antibody-mediated rejection and for antibody desensitization before transplantation in patients without amyloidosis. On the other hand, treatment with the anti–plasma cell immunomodulatory agent lenalidomide (and others in the “imid” class) has been temporally associated with rejection episodes in multiple case reports and should be avoided after transplantation if possible ( 14 ).…”

Supportive Care in AL Amyloidosis

“…With this sequential approach, an overall survival up to 90% at 1 year and 60% at 5 years has been reported [40, 44]. In case of progression of the underlying plasma cell dyscrasia, the use of immunomodulatory drugs as rescue therapy has been associated with a potential risk of organ rejection [46].…”