Acquired amegakaryocytic thrombocytopenia after durvalumab administration

Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destructi...

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Published inJournal of Clinical and Experimental Hematopathology Vol. 61; no. 1; pp. 53 - 57
Main Authors Suyama, Takahiro, Hagihara, Masao, Kubota, Naoto, Osamura, Yoshiyuki, Shinka, Yoko, Miyao, Naoki
Format Journal Article
LanguageEnglish
Published Japan The Japanese Society for Lymphoreticular Tissue Research 01.01.2021
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Abstract Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 104/μL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 104/μL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (< 1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.
AbstractList Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 10 /μL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 10 /μL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (< 1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.
Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 10 4 /μL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 10 4 /μL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (< 1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.
Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 104/μL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 104/μL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (<1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.
Author Suyama, Takahiro
Osamura, Yoshiyuki
Miyao, Naoki
Shinka, Yoko
Hagihara, Masao
Kubota, Naoto
AuthorAffiliation 1) Departments of Internal Medicine and 3) Pathology, Nippon Koukan Hospital , Kawasaki, Kanagawa , Japan , 2) Department of Hematology, Eiju General Hospital, Taito , Tokyo , Japan , 4) Department of Pathology , Keio University School of Medicine , Tokyo , Japan
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  fullname: Miyao, Naoki
  organization: Departments of Internal Medicine,Nippon Koukan Hospital, Kawasaki, Kanagawa, Japan
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Cites_doi 10.21873/invivo.11852
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10.2217/imt-2017-0100
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Keywords acquired amegakaryocytic thrombocytopenia
immune-related thrombocytopenia
durvalumab
immune checkpoint inhibitor
eltrombopag
Language English
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11 Pföhler C, Eichler H, Burgard B et al. A case of immune thrombocytopenia as a rare side effect of an immunotherapy with PD1-blocking agents for metastatic melanoma. Transfus Med Hemother. 2017; 44: 426-428.
1 Calvo R. Hematological side effects of immune checkpoint inhibitors: the example of immune-related thrombocytopenia. Front Pharmacol. 2019; 10: 454.
7 Kanameishi S, Otsuka A, Nonomura Y et al. Idiopathic thrombocytopenic purpura induced by nivolumab in a metastatic melanoma patient with elevated PD-1 expression on B cells. Ann Oncol. 2016; 27: 546-547.
8 Le Roy A, Kempf E, Ackermann F et al. Two cases of immune thrombocytopenia associated with pembrolizumab. Eur J Cancer. 2016; 54: 172-174.
2 Delanoy N, Michot JM, Comont T et al. Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study. Lancet Haematol. 2019; 6: e48-e57.
3 Young A, Quandt Z, Bluestone JA. The balancing act between cancer immunity and autoimmunity in response to immunotherapy. Cancer Immunol Res. 2018; 6: 1445-1452.
5 Kopecký J, Trojanová P, Kubeček O, Kopecký O. Treatment possibilities of ipilimumab-induced thrombocytopenia—case study and literature review. Jpn J Clin Oncol. 2015; 45: 381-384.
9 Le Burel S, Champiat S, Mateus C et al. Prevalence of immune-related systemic adverse events in patients treated with anti-Programmed cell Death 1/anti-Programmed cell Death-Ligand 1 agents: A single-centre pharmacovigilance database analysis. Eur J Cancer. 2017; 82: 34-44.
12 Shiuan E, Beckermann KE, Ozgun A et al. Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy. J Immunother Cancer. 2017; 5: 8.
20 Benedetti F, de Sabata D, Perona G. T suppressor activated lymphocytes (CD8 + /DR +) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. Stem Cells. 1994; 12: 205-213.
13 Jotatsu T, Oda K, Yamaguchi Y et al. Immune-mediated thrombocytopenia and hypothyroidism in a lung cancer patient treated with nivolumab. Immunotherapy. 2018; 10: 85-91.
4 Ahmad S, Lewis M, Corrie P, Iddawela M. Ipilimumab-induced thrombocytopenia in a patient with metastatic melanoma. J Oncol Pharm Pract. 2012; 18: 287-292.
19 Gewirtz AM, Sacchetti MK, Bien R, Barry WE. Cell-mediated suppression of megakaryocytopoiesis in acquired amegakaryocytic thrombocytopenic purpura. Blood. 1986; 68: 619-626.
14 Hasegawa T, Ozaki Y, Inoue T et al. Nivolumab-related severe thrombocytopenia in a patient with relapsed lung adenocarcinoma: a case report and review of the literature. J Med Case Reports. 2019; 13: 316.
23 Mukai HY, Kojima H, Todokoro K et al. Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost. 1996; 76: 675-678.
10 Karakas Y, Yuce D, Kılıckap S. Immune thrombocytopenia induced by nivolumab in a metastatic non-small cell lung cancer patient. Oncol Res Treat. 2017; 40: 621-622.
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15 Mori H, Sakai C, Iwai M et al. Immune thrombocytopenia induced by nivolumab in a patient with non-small cell lung cancer. Respir Med Case Rep. 2019; 28: 100871.
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17 Kuwana M, Okazaki Y, Kajihara M et al. Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis Rheum. 2002; 46: 2148-2159.
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References_xml – reference: 20 Benedetti F, de Sabata D, Perona G. T suppressor activated lymphocytes (CD8 + /DR +) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. Stem Cells. 1994; 12: 205-213.
– reference: 21 Agarwal N, Spahr JE, Werner TL, Newton DL, Rodgers GM. Acquired amegakaryocytic thrombocytopenic purpura. Am J Hematol. 2006; 81: 132-135.
– reference: 10 Karakas Y, Yuce D, Kılıckap S. Immune thrombocytopenia induced by nivolumab in a metastatic non-small cell lung cancer patient. Oncol Res Treat. 2017; 40: 621-622.
– reference: 18 Kuwana M, Kaburaki J, Okazaki Y, Miyazaki H, Ikeda Y. Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus. Rheumatology. 2006; 45: 851-854.
– reference: 23 Mukai HY, Kojima H, Todokoro K et al. Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost. 1996; 76: 675-678.
– reference: 7 Kanameishi S, Otsuka A, Nonomura Y et al. Idiopathic thrombocytopenic purpura induced by nivolumab in a metastatic melanoma patient with elevated PD-1 expression on B cells. Ann Oncol. 2016; 27: 546-547.
– reference: 1 Calvo R. Hematological side effects of immune checkpoint inhibitors: the example of immune-related thrombocytopenia. Front Pharmacol. 2019; 10: 454.
– reference: 2 Delanoy N, Michot JM, Comont T et al. Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study. Lancet Haematol. 2019; 6: e48-e57.
– reference: 3 Young A, Quandt Z, Bluestone JA. The balancing act between cancer immunity and autoimmunity in response to immunotherapy. Cancer Immunol Res. 2018; 6: 1445-1452.
– reference: 11 Pföhler C, Eichler H, Burgard B et al. A case of immune thrombocytopenia as a rare side effect of an immunotherapy with PD1-blocking agents for metastatic melanoma. Transfus Med Hemother. 2017; 44: 426-428.
– reference: 4 Ahmad S, Lewis M, Corrie P, Iddawela M. Ipilimumab-induced thrombocytopenia in a patient with metastatic melanoma. J Oncol Pharm Pract. 2012; 18: 287-292.
– reference: 5 Kopecký J, Trojanová P, Kubeček O, Kopecký O. Treatment possibilities of ipilimumab-induced thrombocytopenia—case study and literature review. Jpn J Clin Oncol. 2015; 45: 381-384.
– reference: 9 Le Burel S, Champiat S, Mateus C et al. Prevalence of immune-related systemic adverse events in patients treated with anti-Programmed cell Death 1/anti-Programmed cell Death-Ligand 1 agents: A single-centre pharmacovigilance database analysis. Eur J Cancer. 2017; 82: 34-44.
– reference: 6 Bagley SJ, Kosteva JA, Evans TL, Langer CJ. Immune thrombocytopenia exacerbated by nivolumab in a patient with non-small-cell lung cancer. Cancer Treat Commun. 2016; 6: 20-23.
– reference: 22 Nishino S, Kodaka T, Sawada Y et al. Marked rebound thrombocytosis in response to glucocorticoids in a patient with acquired amegakaryocytic thrombocytopenia. J Clin Exp Hematop. 2018; 58: 166-170.
– reference: 12 Shiuan E, Beckermann KE, Ozgun A et al. Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy. J Immunother Cancer. 2017; 5: 8.
– reference: 15 Mori H, Sakai C, Iwai M et al. Immune thrombocytopenia induced by nivolumab in a patient with non-small cell lung cancer. Respir Med Case Rep. 2019; 28: 100871.
– reference: 19 Gewirtz AM, Sacchetti MK, Bien R, Barry WE. Cell-mediated suppression of megakaryocytopoiesis in acquired amegakaryocytic thrombocytopenic purpura. Blood. 1986; 68: 619-626.
– reference: 8 Le Roy A, Kempf E, Ackermann F et al. Two cases of immune thrombocytopenia associated with pembrolizumab. Eur J Cancer. 2016; 54: 172-174.
– reference: 17 Kuwana M, Okazaki Y, Kajihara M et al. Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis Rheum. 2002; 46: 2148-2159.
– reference: 16 Mouri A, Kaira K, Shiono A, Miura Y, Kagamu H. Severe thrombocytopenia associated with pembrolizumab in a patients with non-small cell lung cancer (NSCLC): A case report and literature review. In Vivo. 2020; 34: 877-880.
– reference: 14 Hasegawa T, Ozaki Y, Inoue T et al. Nivolumab-related severe thrombocytopenia in a patient with relapsed lung adenocarcinoma: a case report and review of the literature. J Med Case Reports. 2019; 13: 316.
– reference: 13 Jotatsu T, Oda K, Yamaguchi Y et al. Immune-mediated thrombocytopenia and hypothyroidism in a lung cancer patient treated with nivolumab. Immunotherapy. 2018; 10: 85-91.
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Snippet Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most...
Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T cell responses, may cause various immune-related adverse events. Most...
Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most...
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pubmed
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StartPage 53
SubjectTerms acquired amegakaryocytic thrombocytopenia
Case Report
durvalumab
eltrombopag
immune checkpoint inhibitor
immune-related thrombocytopenia
Title Acquired amegakaryocytic thrombocytopenia after durvalumab administration
URI https://www.jstage.jst.go.jp/article/jslrt/61/1/61_20047/_article/-char/en
http://mol.medicalonline.jp/en/journal/download?GoodsID=co8lymph/2021/006101/008&name=0053-0057e
https://www.ncbi.nlm.nih.gov/pubmed/33431742
https://pubmed.ncbi.nlm.nih.gov/PMC8053569
Volume 61
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ispartofPNX Journal of Clinical and Experimental Hematopathology, 2021, Vol.61(1), pp.53-57
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