Durable remission of thrombotic thrombocytopenic purpura in the setting of pembrolizumab therapy

Abstract

Background: There is a small but growing number of thrombotic thrombocytopenic purpura (TTP) cases attributed to immune checkpoint inhibitor therapy, with nivolumab and ipilimumab therapy being the most frequently described in the literature.Study Design and Methods: This report evaluates the course of a patient with a history of metastatic adenocarcinoma of the lung who developed TTP following treatment with the PD-1 inhibitor Pembrolizumab. The patient was treated with six sessions of therapeutic plasma exchange and appeared to be in remission. Exacerbation occurred 4 days later, and seven more sessions of plasma exchange were performed along with four total doses of Rituximab, and a steroid taper with monitoring of platelet counts and ADAMTS13 activity.Results: His platelet count recovered to a peak of 318,000 UL with an ADAMTS13 activity of 77% at the time of discharge. The patient has been following up regularly for outpatient testing with no TTP relapse as of the completion of this report.Discussion: This is one of a few cases of Pembrolizumab-associated TTP reported in the literature with successful complete remission following treatment. Plasma exchange in this setting may be an especially beneficial therapeutic intervention because of the removal of both the anti-ADAMTS13 antibody as well as the immune system upregulating anti-PDL1 monoclonal antibody with replacement of ADAMTS13 from donor plasma. Longer duration of plasma exchange and monitoring for normalization of ADAMTS13 levels in addition to platelet count before cessation of treatment may improve durable remission rates in this entity.

Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management

“…The diagnosis of acquired TTP is made by confirming absence of ADAMTS-13 function and the presence of autoantibodies [ 74 ]. Despite a very high mortality and many patients dying due to TTP, it has been successfully treated with plasmapheresis, corticosteroids, rituximab and caplacizumab [ 47 , 73 , 75 – 77 ].…”