A case of immune thrombocytopaenia induced by pembrolizumab in a metastatic melanoma patient with a history of immune-mediated pure red cell aplasia

Berger, Michel; Amini‐Adlé, Mona; Crumbach, Laura; Dalle, S.

doi:10.1016/j.ejca.2019.02.006

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…Here, we reported the first case of one patient with lung cancer who developed late-onset immune thrombocytopenia during atezolizumab therapy. Similar to this case, delayed toxicity has been observed in other reports, which happened 1 to 2 years after monotherapy ( 26 , 27 ). Generally, other irAEs have been shown to be associated with the efficacy of PD-1/PD-L1 inhibitors in patients with lung cancer ( 28 , 29 ).…”

Section: Epidemiology Of Icis-induced Thrombocytopeniasupporting

confidence: 90%

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

Xie

Cao

2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs), including antibodies targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1), are being extensively used on advanced human malignancies therapy. The treatment with ICIs have acquired durable tumor inhibition and changed the treatment landscape in lung cancer. Immune-related adverse events including pneumonitis and thyroiditis have been well described, but less frequent events, such as ICIs-induced thrombocytopenia, are now emerging and may sometimes be severe or fatal. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff is aware of these potential toxicities and learn to recognize and treat them adequately. This review focuses on the epidemiology, clinical presentation, mechanisms, and clinical management of ICIs-induced thrombocytopenia in patients with lung cancer. We also present a patient with advanced lung adenocarcinoma who received the PD-L1 inhibitor atezolizumab and eventually developed severe thrombocytopenia. The case indirectly suggests that cytokine changes might contribute to immune dysregulation in ICIs-induced thrombocytopenia.

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Section: Epidemiology Of Icis-induced Thrombocytopeniasupporting

confidence: 90%

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

Xie

Cao

2021

Front. Immunol.

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“…No repigmentation was observed. Vitiligo was associated with other skin toxicities in 7 (43.8%) patients and two grade 3 toxicities including a case of auto‐immune red cell aplasia (described in and a case of Vogt–Koyanaga–Harada‐like syndrome (previously reported in the literature). In both grade 3 toxicities, anti‐PD‐1 was definitively interrupted.…”

Section: Resultsmentioning

confidence: 87%

Cutaneous adverse events: a predictor of tumour response under anti‐PD‐1 therapy for metastatic melanoma, a cohort analysis of 189 patients

Bottlaender

Amini‐Adlé

Maucort‐Boulch

et al. 2020

Acad Dermatol Venereol

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Introduction Cutaneous adverse events (AEs) are the most prevalent toxicity under checkpoint inhibitors in clinical trials. In ‘real‐life’ conditions of use, skin toxicities under anti‐PD‐1 have not been described to date in a large cohort. The objective of this study was to determine the clinical features of skin toxicities in patients with advanced melanoma receiving anti‐PD‐1 therapy under ‘real‐life’ conditions of use. Secondary objectives were to evaluate the characteristics of patients with skin toxicities and to analyse associated extra‐cutaneous toxicities, progression‐free survival (PFS) and overall survival (OS). Patients and methods Advanced melanoma patients treated with nivolumab or pembrolizumab between August 2014 and October 2017 were included. Patients lost to follow‐up or receiving anti‐PD‐1 as part of a clinical trial were excluded. Results One hundred and eighty‐nine patients with metastatic melanoma (with 109 men (57.7%) were included. Cutaneous AE occurred in 39 patients (20.6%). The three most prevalent cutaneous AEs were skin eruption (macular–papular or eczematous) (n = 18, 9.5%), vitiligo (n = 16; 8.5%) and isolated pruritus (n = 5, 2.6%). Grade 3–4 skin toxicity was diagnosed in five patients (2.6%). Atopy (28.2% vs. 12.0%; P = 0.024), hypereosinophilia (20.5% vs. 8.7%; P = 0.046), thyroiditis (17.9% vs. 4.7%; P = 0.011) and renal toxicity (15.4% vs. 4%; P = 0.019) were significantly associated with cutaneous AE. Patients with skin eruption (log‐rank = 0.001), vitiligo (log‐rank = 0.001) and any type of cutaneous AE (log‐rank < 0.001) had a better overall survival. Conclusions Cutaneous AEs are frequent and often manageable toxicity and were a predictor of tumour response in melanoma patients under anti‐PD‐1 therapy in this cohort.

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“…In a majority of reported cases, thrombocytopenia occurred as early as initial 1-2 cycles of treatment (5). Our and other case reports showed that it also could develop as a delayed toxicity in which thrombocytopenia happened after approximately 1-2 years of treatment (12,21). Data from the VigiBase showed that immune thrombocytopenic purpura may develop at any time point with a median of 41 days (range from 14 to 321 days) (4).…”

Section: Incidence and Onset Of Immune Thrombocytopenia Induced By Icismentioning

confidence: 64%

“…Although ICIs have been approved for treating various types of human malignancies, immune-related thrombocytopenia is most likely to be reported in NSCLC (5-11, 24, 25), melanoma (12)(13)(14)(15)(16)(17)(18)(19)(20), lymphoma (21), pancreatic cancer (22), and renal cell carcinoma (23), which is consistent with retrospective data from multiple institutions (26). Previous case and retrospective studies show that immune thrombocytopenia occurred in cancer patients treated with PD-1 inhibitor monotherapy, such as nivolumab or pembrolizumab, or a CTLA-4 inhibitor, or a combination with PD-1 and a CTLA-4 inhibitor ( Table 1).…”

Section: Incidence and Onset Of Immune Thrombocytopenia Induced By Icismentioning

confidence: 99%

Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitors in Solid Cancer: Case Report and Literature Review

Liu

Liang²,

Liang

et al. 2020

Front. Oncol.

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Immune checkpoint inhibitors, including antibodies targeting programmed cell death protein-1 (PD-1) and its receptor programmed cell death ligand-1 (PD-L1), represent promising therapeutic strategies for advanced human malignancies. However, a subgroup of patients experiences various autoimmune toxicities, termed immune-related adverse events (irAEs), that occur as a result of on-target and off-tumor autoimmune responses. Although irAEs are generally confirmed to be less severe than toxicities caused by conventional chemotherapy and targeted therapy, uncommon irAEs, such as immune thrombocytopenia, may occur with a very low incidence and sometimes be severe or fatal. This review focuses on the epidemiology, clinical presentation, and prognosis of immune thrombocytopenia occurring in advanced cancer patients induced by immune checkpoint inhibitors, especially in those with PD-1 or PD-L1 inhibitor treatment. We also first present one patient with non-small cell lung cancer who received the PD-L1 inhibitor durvalumab and developed severe thrombocytopenia.

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A case of immune thrombocytopaenia induced by pembrolizumab in a metastatic melanoma patient with a history of immune-mediated pure red cell aplasia

Cited by 8 publications

References 11 publications

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

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

Cutaneous adverse events: a predictor of tumour response under anti‐PD‐1 therapy for metastatic melanoma, a cohort analysis of 189 patients

Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitors in Solid Cancer: Case Report and Literature Review

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