Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival

Haddad, Tyler; Zhao, Songzhu; Li, Mingjia; Patel, Sandip; Johns, Andrew; Grogan, Madison; Lopez, G.; Miah, Abdul; Wei, Lai; Tinoco, Gabriel; Riesenberg, Brian; Li, Zihai; Bertino, Erin M.; Kendra, Kari; Presley, Carolyn J.; Owen, Dwight H.

doi:10.1007/s00262-021-03068-2

Cited by 18 publications

(16 citation statements)

References 45 publications

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“…In addition, anti-PD-(L)1 monotherapy was implicated in 62.0% of hematologic irAEs after ICI treatment in VigiBase ® [ 7 ]. Conversely, ITP incidence appeared highest among those treated with ICI combination approaches in two retrospective studies [ 27 , 28 ]. Whether ICI combination or type of ICI could influence time to onset of hematological irAEs also remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database

Martin

Nguyen

Beuvon

et al. 2022

Cancers

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Immune checkpoint inhibitor (ICI)-related cytopenias have been poorly described. This study aimed to further characterize ICI-related cytopenias, using the French pharmacovigilance database. All grade ≥ 2 hematological adverse drug reactions involving at least one ICI coded as suspected or interacting drug according to the World Health Organization criteria and reported up to 31 March 2022, were extracted from the French pharmacovigilance database. Patients were included if they experienced ICI-related grade ≥ 2 cytopenia. We included 68 patients (75 ICI-related cytopenias). Sixty-three percent were male, and the median age was 63.0 years. Seven patients (10.3%) had a previous history of autoimmune disease. Immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) were the most frequently reported (50.7% and 25.3%, respectively). The median time to onset of ICI-related cytopenias was 2 months. Nearly half were grade ≥ 4, and three patients died from bleeding complications of refractory ITP and from thromboembolic disease with active AIHA. Out of 61 evaluable responses, complete or partial remission was observed after conventional treatment in 72.1% of ICI-related cytopenias. Among the 10 patients with ICI resumption after grade ≥ 2 ICI-related cytopenia, three relapsed. ICI-related cytopenias are rare but potentially life-threatening. Further studies are needed to identify risk factors of ICI-related cytopenias.

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database

Martin

Nguyen

Beuvon

et al. 2022

Cancers

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“…A previous study revealed that the production of platelet-associated immunoglobulin G (PA-IgG) is stimulated by PD-1 or PD-L1 inhibitors, which can block the immunoinhibitory effect of PD-1 on T cells, while the basic underlying pathophysiology of ITP is Fc gamma receptor (FcgR)-mediated phagocytosis via the targeting PA-IgG (20). Moreover, immune thrombocytopenia was found to be associated with worse overall survival in a recent retrospective study (21). The excessive stimulation of PD-1/PD-L1 signaling may develop into ITP and promote platelet destruction.…”

Section: Discussion Of Immunology Specialistmentioning

confidence: 99%

“…Shiuan et al reviewed 2,360 patients with melanoma treated with immune checkpoint inhibitor and identified eleven cases (0.47%) that developed immune thrombocytopenia (16). Haddad et al, who retrospectively reviewed 1,038 patients treated with immune checkpoint inhibitor monotherapy or in combination therapy, found that 1.73% developed grade 3 or higher immune thrombocytopenia (21). Expert opinion 2: Satoru Miura Presumably, biomarkers have been discovered to predict thrombocytopenia as an irAE.…”

Section: Question 4: What Is the Current Research Progress On The Inc...mentioning

confidence: 99%

Immune thrombocytopenia in a small cell lung cancer patient treated with atezolizumab: a case report

Qiu¹,

Li²,

Li³

et al. 2022

Transl Lung Cancer Res

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Background: Immune checkpoint inhibitors (ICIs), an enormous oncological breakthrough in the last 10 years, have become the standard treatments for several types of solid cancers. Although ICIs are generally well tolerated and result in favorable outcomes, they also cause unique immune-related adverse events (irAEs) across bodily systems and organs. Compared to most common irAEs, which occur in the endocrine, skin, pulmonary system, and gastrointestinal tract, haematological irAEs (haem-irAEs) are relatively rare but potentially life-threatening events that are occasionally irreversible and refractory. Currently, haem-irAEs are not sufficiently understood, management, and lack consensus, while other common irAEs have well been characterized and managed. The reports of ICI-related thrombocytopenia in small cell lung cancer (SCLC) are rarely seen. Hence, we reported a rare case of severe steriod-resistant ICI-related thrombocytopenia after received chemotherapy plus anti-PD-L1 inhibitor in SCLC patient. Our case exemplifies the diagnosis, diagnosis of exclusion, treatment, and prognosis of thrombocytopenia in the pattern of combination therapy, meanwhile, the subject of diagnosis, therapies, therapeutic strategies for refractory type and incidence, potential biomarkers, mechanisms and prognosis in ICI-related thrombocytopenia have been fully discussed.Case Description: Herein, we present a 64-year-old man diagnosed advanced SCLC developed refractory immune-related severe thrombocytopenia, who achieved favorable outcomes of cancer following chemotherapy combined with atezolizumab administrated. Routine blood re-examination on the third day of 6th therapy showed a thrombocyte count of 11×10 9 /L. Combined the medical history and the results of laboratory tests, the diagnosis of ICI-induced thrombocytopenia was confirmed. Despite large doses of methylprednisolone, immunoglobulin, and rituximab, intermittent platelet transfusion, thrombopoietin being administrated to the patient, there were no signs of platelet count and hemoglobin improvement.Currently, this is the first case about atezolizumab induced thrombocytopenia in SCLC patient, while there is extremely rare haem-irAEs reported in SCLC.Conclusions: Although ICI-related severe thrombocytopenia is rare, it may persist or even be fatal. Clinicians should pay more attention to its diagnosis and prompt treatment. Once developed thrombocytopenia, large doses of methylprednisolone, ntermittent platelet transfusion, thrombopoietin should be timely administrated, also plasma exchange or rilzabrutinib, other immunosuppressive drugs, or IL-6 inhibitor warrant apply if steriod-resistant.

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“… 18 This condition is rare, with an incidence between 0.2% to 2.8%, and is almost never severe or fatal. 19 …”

Section: Immune Thrombocytopenia Induced By Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Treatment of drug-induced immune thrombocytopenias

et al. 2022

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Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct toxicity of drug molecules to platelets or megakaryocytes. Immune-mediated thrombocytopenia, on the other hand, involves the formation of antibodies that react to platelet-specific glycoprotein complexes, as in classic drug-induced immune thrombocytopenia (DITP), or to platelet factor 4, as in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Clinical signs include a rapid drop in platelet count, bleeding or thrombosis. Since the patient's condition can deteriorate rapidly, prompt diagnosis and management are critical. However, the necessary diagnostic tests are only available in specialized laboratories. Therefore, the most demanding step in treatment is to identify the agent responsible for thrombocytopenia, which often proves difficult because many patients are taking multiple medications and have comorbidities that can themselves also cause thrombocytopenia. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management.

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Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival

Cited by 18 publications

References 45 publications

Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database

Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database

Immune thrombocytopenia in a small cell lung cancer patient treated with atezolizumab: a case report

Treatment of drug-induced immune thrombocytopenias

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