Chimeric antigen receptor T cell therapy and nephrotoxicity: From diagnosis to treatment strategies

Zhou, Hua; Cui, Li; Jiang, Jingting

doi:10.1016/j.intimp.2020.107072

Cited by 8 publications

(9 citation statements)

References 79 publications

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“…Indeed, adults with HLH have poor outcomes even with aggressive treatment [ 5 ]. While etoposide treats HLH by inhibiting monocyte-macrophage activation [ 15 ], it is one of the cytotoxic chemotherapies most associated with TLS, especially in the context of hematologic malignancy [ 16 ]. TLS is best prevented rather than managed.…”

Section: Discussionmentioning

confidence: 99%

A Case of Hemophagocytic Lymphohistiocytosis (HLH) Secondary to T Cell Lymphoma and Cytomegalovirus (CMV) Infection and Complicated by Tumor Lysis Syndrome (TLS)

et al. 2022

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Patient: Male, 48-year-old Final Diagnosis: CMV infection • hemophagocytic lymphohistiocytosis (HLH) • lymphoma • tumor lysis syndrome Symptoms: Altered mental state • anasarca • respiratory distress • sepsis • shock • splenomegaly Medication: — Clinical Procedure: — Specialty: Hematology • Immunology • Infectious Diseases • General and Internal Medicine • Oncology Objective: Rare disease Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of systemic hyper-inflammation, caused by an excessive cytokine secretion, secondary to an uncontrolled proliferation of lymphocytes and macrophages, and leading to vascular endothelial injury and multi-organ failure. HLH is either primary/familial due to genetic mutations in the genes coding for the CD8+ and NK T cells cytotoxic proteins or is secondary to infection, malignancy, or autoimmune disorders. Timely diagnosis using the HLH-2004 criteria and prompt initiation of treatment for HLH is essential for the survival of affected patients. Adults with HLH have poor outcomes even with aggressive treatment. Case Report: Our patient was a 48-year-old man who presented with altered mental status. He was tachycardic and tachypneic, and quickly developed acute hypoxemic respiratory failure requiring mechanical ventilation. Computed tomography (CT) of the chest and abdomen showed bilateral pleural effusion, ascites, and heterogeneous splenomegaly. Laboratory workup revealed anemia, thrombocytopenia, severe hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia. Pleural fluid analysis showed a lymphocytic exudate, with T cell predominance on flow cytometry. A T cell rearrangement study of the pleural fluid was positive. Bone marrow biopsy showed histiocytes with hemophagocytic activity. The diagnosis of HLH secondary to T cell lymphoma was made, and the patient was treated with dexamethasone and etoposide. A few hours later, the patient had a cardiac arrest, and laboratory findings suggestive of tumor lysis syndrome (TLS) were discovered. The patient died of refractory shock one day later, and the cytomegalovirus (CMV) PCR result was positive during that day. Conclusions: Adults with HLH have poor outcomes even with aggressive treatment. Additional focus on the management of HLH should shift towards preventing complications such as TLS. More studies should focus on post-treatment outcomes of HLH secondary to malignancy to improve the management and prognosis.

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Section: Discussionmentioning

confidence: 99%

A Case of Hemophagocytic Lymphohistiocytosis (HLH) Secondary to T Cell Lymphoma and Cytomegalovirus (CMV) Infection and Complicated by Tumor Lysis Syndrome (TLS)

et al. 2022

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“…Cellular contents from nontumor cells also occur because of on-target off-tumor toxicity (85). There is a narrow set of tumor-specific antigens that are recognized by CAR-T cells, but in addition, there are tumor-associated antigens, which are weakly expressed in normal tissues and can be damaged as a result of the therapy contributing to hyperphosphatemia (85,88).…”

Section: Hyperphosphatemiamentioning

confidence: 99%

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy

Uppal

Workeneh

Rondon‐Berrios

et al. 2022

CJASN

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Novel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all solid cancers. Immune-related adverse events have been associated with immunotherapies. Acute kidney injury has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations including immune checkpoint inhibitor-induced parathyroid hormone - related peptide production, sarcoid-like granulomas, and hyper-progression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor-induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy-associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.

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“…Renal AEs include AKI related to CRS [ 157 ], related to prerenal and renal mechanisms [ 158 ]. Prerenal AKI after CAR-T treatment is associated with impaired renal perfusion caused predominantly by CRS complications such as fever or vomiting, which may lead to dehydration resulting in a reduction in the intravascular volume [ 159 ].…”

Section: Chimeric Antigen Receptor T Cell (Car-t Cell) Therapymentioning

confidence: 99%

Adverse Renal Effects of Anticancer Immunotherapy: A Review

Borówka

Łącki-Zynzeling

Nicze

et al. 2022

Cancers

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Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines, tumor-targeting monoclonal antibodies (TT-mAbs), bispecific antibodies and cytokine therapy improve patients’ outcomes. However, stimulation of the immune system, beneficial in terms of fighting against cancer, generates the risk of harm to other cells in a patient’s body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, superficially, are renal AEs in patients treated with ICIs. International guidelines issued by the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are fewer data concerning real occurrence and possible presentations of renal adverse drug reactions of other immunotherapeutic methods. This implies the need for the collection of safety data during ongoing clinical trials and in the real-life world to characterize the hazard related to the use of new immunotherapies and management of irAEs.

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Chimeric antigen receptor T cell therapy and nephrotoxicity: From diagnosis to treatment strategies

Cited by 8 publications

References 79 publications

A Case of Hemophagocytic Lymphohistiocytosis (HLH) Secondary to T Cell Lymphoma and Cytomegalovirus (CMV) Infection and Complicated by Tumor Lysis Syndrome (TLS)

A Case of Hemophagocytic Lymphohistiocytosis (HLH) Secondary to T Cell Lymphoma and Cytomegalovirus (CMV) Infection and Complicated by Tumor Lysis Syndrome (TLS)

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy

Adverse Renal Effects of Anticancer Immunotherapy: A Review

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