Case Report: Successful Avatrombopag Treatment for Two Cases of Anti-PD-1 Antibody-Induced Acquired Amegakaryocytic Thrombocytopenia

Abstract

Background: Anti-PD-1/PD-L1 immunotherapy has achieved impressive responses in multiple types of malignancies in recent years. However, immune-related adverse events (irAEs) occur and limit their continuous clinical use. Among these irAEs, acquired amegakaryocytic thrombocytopenia (AAT) is rare but often clinically serious, life-threatening and refractory to multiple treatment approaches.Case summary: We reported for the first time the successful treatment of avatrombopag in two cases of anti-PD1 antibody-induced AAT (in particular, one case had progressed to aplastic anemia), which was refractory or intolerant to glucocorticoids, ciclosporin, intravenous immunoglobulin (IVIG), recombinant human thrombopoietin (rh-TPO) and even TPO receptor agonist (TPO-RA) eltrombopag. To date, the two cases manifested as normal platelet counts and are independent of transfusion.Conclusion: Anti-PD1 antibody-induced AAT occurs with low frequency but is often serious and difficult to manage, for which this study proposed vatrombopag as a potential curative and safe approach.

Effectiveness and Safety of Avatrombopag in Liver Cancer Patients with Severe Thrombocytopenia: Real-World Data and Challenges

“…Such a result might be attributed to the fact that avatrombopag increases only platelet count and does not activate platelets [ 27 ]. Consistent with our results, a recent study reported successful treatment with avatrombopag in two patients bearing urological neoplasms who developed anti-PD1 antibody-induced amegakaryocytic thrombocytopenia and were refractory or intolerant to any other thrombopoietic agents including glucocorticoids, cyclosporine, intravenous immunoglobulin, rh-thrombopoietin, and eltrombopag [ 28 ]. Thus, the present study reproduced the results of clinical trials in the real-world setting, and avatrombopag was considered effective and safe for liver cancer patients with severe thrombocytopenia.…”

Immune checkpoint inhibitor-related acquired amegakaryocytosis thrombocytopenia: a case report and literature review

“…It revealed in all cases an absence of megakaryocytes. The cellularity of bone marrow is variable: clear hypoplasia was found in two patients ( 6 , 8 ), moderate hypocellularity (20%–30%) in one patient, and normal one in two others, including our patient ( 8 ). In a surprising way, lymphocyte T-CD8+ infiltration, classically found in BM biopsy of an AAT patient and in other hem-irAEs such as aplastic anemia, is described only in our case ( 3 , 5 , 13 ).…”

“…The second case published by Tu et al. also suffered from other cytopenia probably caused by secondary aplastic anemia ( 8 ). BM biopsy is important to exclude blast infiltration, dysplasia, aplastic anemia, or fibrosis.…”

“…In the case of Iyama et al., CS was nevertheless stopped after diagnosis of gastric ulcer and so response to steroid was not clear ( 6 ). CSA was used in two patients with complete response, defined as a platelet count ≥100×10 9 /l ( 14 ): alone in one case and associated with TPO-RA in another one ( 6 , 8 ). In the three other cases, complete response was obtained after TPO-RA ( 7 , 8 ).…”

“…CSA was used in two patients with complete response, defined as a platelet count ≥100×10 9 /l ( 14 ): alone in one case and associated with TPO-RA in another one ( 6 , 8 ). In the three other cases, complete response was obtained after TPO-RA ( 7 , 8 ). Both eltrombopag (50 mg daily) and avatrombopag has led to a quick increase of platelet count ( 7 , 8 ).…”