Thrombotic thrombocytopenic purpura associated to dual checkpoint inhibitor therapy for metastatic melanoma

Lafranchi, Anne; Springe, Dirk; Rupp, Adrienne; Ebnöther, Lukas; Zschiedrich, Stefan

doi:10.1007/s13730-020-00454-0

Cited by 21 publications

(17 citation statements)

References 5 publications

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“…We identified one reported case of ICI-induced TMA and four reported cases of ICI-induced TTP (Table 2) [3,[12][13][14][15]. As the causative agents, three were nivolumab and four were ipilimumab, and two cases were combinations of these two drugs.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab-associated thrombotic microangiopathy in a patient with urothelial cancer: a case report and literature review

Hayata

Shimanuki

et al. 2020

Ren Replace Ther

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Background: Pembrolizumab, a highly selective humanized monoclonal IgG4κ isotype antibody against PD-1, is one of the immune checkpoint inhibitors approved for treatment of various cancers. The most frequent immunerelated adverse events include skin, gastrointestinal, and endocrine abnormalities. In rare cases, however, adverse events on the kidney do occur. Case presentation: We here report a case of acute kidney injury presenting thrombocytopenia and hemolytic anemia with the presence of schistocytes, which developed in a 68-year-old man with urothelial cancer, 7 months after initiation of pembrolizumab treatment (10 cycles) and 3 weeks after treatment cessation. The patient had previously undergone unilateral nephrectomy and prior treatment with combined gemcitabine and carboplatin regimen. Although corticosteroid, hemodialysis, and plasma exchange were initiated, the patient died within a few days of respiratory failure. Pathological examination at autopsy revealed multiple carcinomas including the lung, liver, and spine, together with the diagnosis of thrombotic microangiopathy by electron microscopy findings of the renal tissue. To our knowledge, this is the first report describing severe thrombotic microangiopathy in a patient possibly associated with pembrolizumab, leading to death. Conclusion: Physicians should be aware of this potential side effect in patients presenting acute kidney injury and thrombocytopenia.

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Section: Discussionmentioning

confidence: 99%

Pembrolizumab-associated thrombotic microangiopathy in a patient with urothelial cancer: a case report and literature review

Hayata

Shimanuki

et al. 2020

Ren Replace Ther

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“…In total, six cases of ICI-associated TTP have been reported (Table 2) [5][6][7][8][9][10]. There was only one other case of pembrolizumab-associated TTP; however, we did find an additional case of pembrolizumab-associated TMA [5,15].…”

Section: Discussionmentioning

confidence: 64%

“…Herein, we present a case of ICI-associated thrombotic thrombocytopenic purpura (TTP) in a 61-year-old man with advanced NSCLC who was treated with pembrolizumab. Only six other cases of ICI-related TTP have been reported to date [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Associated Thrombotic Thrombocytopenic Purpura in a Patient With Metastatic Non-Small-Cell Lung Cancer

Filippis¹,

Moore²,

Ezell³

et al. 2021

Cureus

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Background: Immune-related adverse events (irAEs) are secondary reactions related to treatment with immune checkpoint inhibitors (ICIs). There have been six cases published reporting on an association between patients undergoing treatment with ICIs and the occurrence of acquired thrombotic thrombocytopenic purpura (TTP).Case report: We report a 61-year-old male receiving treatment with chemoimmunotherapy followed by pembrolizumab maintenance therapy for advanced non-small-cell lung cancer, presenting with bleeding symptoms, anemia, and thrombocytopenia. The patient received pembrolizumab seven times in total, in three-week cycles. Laboratory testing demonstrated hemolytic anemia, which, in combination with other findings, suggested thrombotic microangiopathy (TMA). PLASMIC scoring and specialized testing with ADAMTS13 activity and inhibitor confirmed a diagnosis of TTP. The patient was started on therapy with plasmapheresis and glucocorticoids, resulting in clinical improvement. The patient chose to leave the hospital under the care of home hospice and died approximately one month after being discharged.Conclusions: Of the six cases of ICI-induced TTP, only one other was treated with pembrolizumab to our knowledge to date. Our patient experienced an adverse reaction marked by thrombocytopenia and hematuria after drug exposure. With symptom improvement after ICI discontinuation and recurrence on readministration, a presumptive diagnosis of ICI-associated TTP was made. This case report and literature review emphasize the need for close observation of patients undergoing ICI therapy for potential rare irAEs. The further investigation aimed at the study of risk factors, disease severity, and treatment response to this form of secondary TTP is needed to guide treatment decisions.

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“…This leads to an excess of vWF-causing platelet aggregation, causing small vessel thrombi and organ damage. There are four case reports of TTP due to ICIs (Dickey et al, 2020; King et al, 2017 ; Lafranchi et al, 2020 ; Youssef et al, 2018 ). The classic pentad for the diagnosis of TTP is fever, hemolytic anemia, thrombocytopenia, renal impairment, and neurologic manifestations; however, this pentad may be misleading since it has been identified when TTP is largely fatal due to lack of effective treatment.…”

Section: Thrombocytopeniamentioning

confidence: 99%

Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors

Rogers

Zawislak

Wong

2021

JADPRO

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Immune checkpoint inhibitors target suppressor receptors, including cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The activated T cells are not antigen specific; therefore, the blockade of the immune checkpoint may result in the development of autoimmune adverse events. The most common immune-related adverse events (irAEs) are rash, colitis, and endocrinopathies. However, irAEs that affect the hematologic system are rare and can affect red blood cells (e.g., autoimmune hemolytic anemia), white blood cells, and platelets (e.g., immune thrombocytopenia). Usually one cell line is affected; however, in some cases, multiple cell lines can be affected. Other changes in the hematologic system can also be affected (e.g., cryoglobulinemia, cytokine release syndrome). Due to the rarity and lack of recognition of these AEs, the timing, spectrum of events, and clinical presentation are poorly understood. Management of hematologic irAEs usually involves the use of steroids; however, other agents (e.g., IVIG, cyclosporine, rituximab) or procedures (e.g., plasma exchange, transfusions) can also be used.

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Thrombotic thrombocytopenic purpura associated to dual checkpoint inhibitor therapy for metastatic melanoma

Cited by 21 publications

References 5 publications

Pembrolizumab-associated thrombotic microangiopathy in a patient with urothelial cancer: a case report and literature review

Pembrolizumab-associated thrombotic microangiopathy in a patient with urothelial cancer: a case report and literature review

Immune Checkpoint Inhibitor-Associated Thrombotic Thrombocytopenic Purpura in a Patient With Metastatic Non-Small-Cell Lung Cancer

Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors

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