Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

Xie, Wang; Hu, Nana; Cao, Lejie

doi:10.3389/fimmu.2021.790051

Cited by 17 publications

(16 citation statements)

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“…Previous studies have shown that the change in the frequency of T cells, particularly for Tregs, is associated with the pathogenesis of irAEs ( 23 , 35 ). Recent studies have noted that high levels of pro-inflammatory cytokines may contribute to the pathogenesis of irAEs ( 18 , 26 , 27 ). In this study, we found that combination of CAIA and ICI, but not their alone, caused significantly higher frequency of TNF-α secreting CD4 + and CD8 + T cells and higher percentages of effector memory T cells, but not IFN-γ, IL-4, and IL-17 secreting T cells and Tregs, in the circulation and peripheral lymph organs as well as in the lungs of humanized mice.…”

Section: Discussionmentioning

confidence: 99%

“…For example, many pro-inflammatory effectors and memory T cells infiltrate the targeted tissues and organs ( 22 – 24 ). Recently, some investigations have reported that high levels of pro-inflammatory IL-6, IL-17 and GM-CSF secretion may contribute to the onset of irAEs ( 25 – 27 ). However, what types of effector T cells are and how they mediate the onset of irAEs have not been clarified, particularly for the ICI-related arthritis and pneumonitis in humans.…”

Section: Introductionmentioning

confidence: 99%

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TNF-α inhibitor ameliorates immune-related arthritis and pneumonitis in humanized mice

et al. 2022

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ObjectivesThis study aimed at establishing a mouse model of immune-related adverse in humanized BALB/c-hPD1/hCTLA4 mice to investigate their potential pathogenesis and explore therapeutic targets for immune-related arthritis and pneumonitis.MethodsHumanized BALB/c-hPD1/hCTLA4 mice were injected with vehicle or collagen-specific antibodies (CA) and immune checkpoint inhibitors (ICI, ipilimumab, anti-human CTLA-4; and nivolumab, anti-human PD-1), and some mice were treated with anti-TNF-α antibody, leading to the control, collagen antibody-induced arthritis (CAIA), CAIA+ICI and treatment groups. The severity of clinical arthritis and pneumonitis in mice was monitored longitudinally and the pathological changes in the joints and lungs were histologically analyzed and the contents of lung hydroxyproline were measured. The frequency of different subsets of T cells was analyzed by flow cytometry and multiplex immunofluorescency.ResultsCompared with the control, the ICI group of mice developed the delayed onset of moderate degrees of arthritis while the CAIA+ICI group of mice exhibited the early onset of severe arthritis. Treatment with ICI caused severe pneumonitis, especially in the mice with CA. Flow cytometry analysis indicated a significantly higher frequency of splenic TNF-α+CD4+ and TNF-α+CD8+ T cells, but not other subsets of T cells tested, in the CAIA+ICI group of mice, relative to that in other groups of mice. Treatment with anti-TNF-α significantly mitigated the severity of arthritis and pneumonitis as well as deposition of collagen in lung of mice. The treatment also decreased the frequency of TNF-α+CD4+ and TNF-α+CD8+ T cells as well as effector memory T cells in the periphery lymph orangs and lungs of mice.ConclusionsWe successfully established a humanized mouse model of ICI-related severe arthritis and pneumonitis with a higher frequency of TNF-α+ T cells, which were significantly mitigated by anti-TNF-α treatment. Conceptually, ICI treatment can induce multiple autoimmune-like diseases in autoimmune-prone individuals and TNF-α+ T cells may be therapeutic targets for intervention of immune-related arthritis and pneumonitis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TNF-α inhibitor ameliorates immune-related arthritis and pneumonitis in humanized mice

et al. 2022

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“…Unfortunately, large doses of methylprednisolone, immunoglobulin and rituximab, intermittent platelet transfusion, thrombopoietin, and hemoglobinogen being administered to the patient, and his conditions did not improve. (17), and ICI induced thrombocytopenia in only one case of SCLC (7). Haem-irAEs have not only been poorly understood and described but also lack consensus, whereas other common irAEs have well been characterized and managed.…”

Section: Discussion Among Physicians From the First Affiliated Hospit...mentioning

confidence: 99%

“…Isolated case reports and case series have presented the hematologic toxicities induced by ICIs, but the incidence, diagnosis, and biological mechanisms in such patients remain unclear ( 7 - 17 ). Previous reports have summarized immune thrombocytopenia induced by immune checkpoint inhibitors in lung cancer ( 17 ), and ICI induced thrombocytopenia in only one case of SCLC ( 7 ). Haem-irAEs have not only been poorly understood and described but also lack consensus, whereas other common irAEs have well been characterized and managed.…”

Section: Imdt Discussionmentioning

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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“…Tis situation is more complicated in liver cancer, which is the sixth most frequent cancer types and the fourth leading cause of cancer-related mortality globally because invasive therapeutic procedures [3], including hepatectomy, radiofrequency ablation, and biopsy, carry additional hemorrhage risk. Besides, for patients who receive systemic therapy, thrombocytopenia is not a rare event due to myelotoxicity or immunotherapy-related myelosuppression [4][5][6], resulting in chemotherapy dose reduction, prolonged interval between treatment cycles, or shifting to less-intensive regimens with the risk of a decreasing response rate and overall survival. Under such circumstances, thrombopoietic drugs, such as corticosteroids and recombinant human thrombopoietin, or platelet transfusion are often prescribed [7].…”

Section: Introductionmentioning

confidence: 99%

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

Huang

Chen

et al. 2022

Journal of Oncology

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Background. Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 109/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown. Methods. Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled. Avatrombopag dose, peak and absolute platelet count increase, combination treatment with other thrombopoietic agents, responder (peak count ≥50 × 109/L with absolute increase ≥20 × 109/L) rate, and anticancer treatment effect were analyzed. Thrombosis and bleeding events were assessed. Results. In total, 93 patients were enrolled, with 72 and 21 in the CLD and non-CLD groups, respectively. Patients with CLD had hepatitis B or C, larger spleen volume, and a higher cirrhosis degree. Baseline platelet counts were similar between two groups (median, 37.0 × 109/L vs. 39.0 × 109/L; P = 0.594 ), while patients without CLD had higher peak platelet (median, 134.0 × 109/L vs. 74.0 × 109/L; P = 0.015 ) and absolute increase (median, 101.0 × 109/L vs. 41.0 × 109/L; P = 0.020 ) after avatrombopag treatment. The responder rate was higher in patients without CLD (100% vs. 76.4%; P = 0.010 ). Combined avatrombopag with other thrombopoietic agents significantly increased platelet count; repeated use of avatrombopag produced similar effects with that of initial treatment. Concerning anticancer treatment effect, patients who responded to avatrombopag had a higher disease control rate. No thrombosis or hemorrhagic events were observed, even in patients with portal vein tumor thrombosis. Conclusion. Avatrombopag was safe and effective and ensured successful implementation of anticancer treatment in liver cancer patients with severe thrombocytopenia, accompanied with or without CLD.

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Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

Cited by 17 publications

References 40 publications

TNF-α inhibitor ameliorates immune-related arthritis and pneumonitis in humanized mice

TNF-α inhibitor ameliorates immune-related arthritis and pneumonitis in humanized mice

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

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

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