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Frontiers in Immunology 2023B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However,...
Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma.
BACKGROUND AIMS
B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.
METHODS
Patients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.
RESULTS
Eighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3-4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5-8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3-10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.
CONCLUSION
TLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.
Topics: Humans; Multiple Myeloma; Receptors, Chimeric Antigen; B-Cell Maturation Antigen; Tumor Lysis Syndrome; Incidence; Creatinine; Prognosis; Cell- and Tissue-Based Therapy
PubMed: 37215107
DOI: 10.3389/fimmu.2023.1125357 -
CMAJ : Canadian Medical Association... Apr 2023
Topics: Humans; Tumor Lysis Syndrome
PubMed: 37040999
DOI: 10.1503/cmaj.221433 -
World Journal of Critical Care Medicine May 2015Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or... (Review)
Review
Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or spontaneously. Clinicians should stratify every hospitalized cancer patient and especially those receiving chemotherapy for the risk of tumor lysis syndrome. Several aspects of prevention include adequate hydration, use of uric acid lowering therapies, use of phosphate binders and minimization of potassium intake. Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders, use of uric acid lowering agents and dialysis in refractory cases.
PubMed: 25938028
DOI: 10.5492/wjccm.v4.i2.130 -
Journal of Oncology 2017Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly... (Review)
Review
Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly non-Hodgkin's lymphoma and acute leukemia due to chemotherapy or spontaneously. It is characterized by a biochemical abnormality such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and its clinical outcome is directly related to these biochemical abnormalities. Prevention and treatment of tumor lysis syndrome depend on immediate recognition of patients at risk. Therefore, identifying patients at risk and prophylactic measures are important to minimize the clinical consequences of tumor lysis syndrome. Patients with low risk should receive hydration and allopurinol. On the other hand patients with high risk should receive hydration and rasburicase in an inpatient setting. It is important to start therapy immediately, to correct all parameters before cancer treatment, to assess risk level of patients for TLS, and to select treatment options based on the risk level. In this review a comprehensive search of literatures was performed using MEDLINE/PubMed, Hinari, the Cochrane library, and Google Scholar to summarize diagnostic criteria, incidence, predicting factors, prevention, and treatment options for tumor lysis syndrome in patients with hematological malignancies.
PubMed: 29230244
DOI: 10.1155/2017/9684909 -
Seminars in Interventional Radiology Jun 2015The rapid expansion of minimally invasive image-guided procedures has led to their extensive use in the interdisciplinary management of patients with vascular,... (Review)
Review
The rapid expansion of minimally invasive image-guided procedures has led to their extensive use in the interdisciplinary management of patients with vascular, hepatobiliary, genitourinary, and oncologic diseases. Given the increased availability and breadth of these procedures, it is important for physicians to be aware of common complications and their management. In this article, the authors describe management of select common complications from interventional radiology procedures including tumor lysis syndrome, acute on chronic postprocedural pain, and venous thromboembolism. These complications are discussed in detail and their medical management is outlined according to generally accepted practice and evidence from the literature.
PubMed: 26038627
DOI: 10.1055/s-0035-1549379 -
Journal of Medical Case Reports Feb 2022Tumor lysis syndrome is an oncologic emergency that classically occurs following cancer therapy, although spontaneous tumor lysis syndrome can also occur in... (Review)
Review
BACKGROUND
Tumor lysis syndrome is an oncologic emergency that classically occurs following cancer therapy, although spontaneous tumor lysis syndrome can also occur in malignancies, albeit rarely. Spontaneous tumor lysis syndrome has previously been reported in some hematologic malignancies, but it rarely happens in solid tumors and seems to be associated with a higher mortality rate. This is the first case of adrenal adenocarcinoma that developed spontaneous tumor lysis syndrome.
CASE PRESENTATION
We present a rare case of spontaneous tumor lysis syndrome occurring in a patient previously diagnosed with adrenal adenocarcinoma. The patient was a 64-year-old Persian man with abdominal pain, hypersomnia, and fatigue who was previously diagnosed with right adrenocortical carcinoma and had undergone right adrenalectomy with regional lymph nodes resection 5 months previously. On physical examination, the patient had abdominal distension and mild tenderness at the right upper quadrant. Pitting edema was detected bilaterally in the lower extremities. Initial imaging revealed multiple and large lesions suggestive of liver metastases. The laboratory data showed hyperkalemia, hyperuricemia, hyperphosphatemia, and elevated serum creatinine level indicative of spontaneous tumor lysis syndrome in the patient. Despite immediate and intensive care with antibiotics, hydration, treatment with a hypouricemic agent, and renal replacement therapy, the patient ultimately died from multiorgan failure.
CONCLUSIONS
Tumor lysis syndrome in solid tumors has high mortality. Patients susceptible to spontaneous tumor lysis syndrome must receive aggressive treatment immediately, which is crucial for preventing morbidity and mortality. Spontaneous tumor lysis syndrome may be underdiagnosed, and a high degree of clinical suspicion is needed to make the diagnosis and proceed with required interventions. Therefore, clinicians should be aware of this rare phenomenon.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Humans; Hyperkalemia; Hyperuricemia; Male; Middle Aged; Tumor Lysis Syndrome
PubMed: 35139902
DOI: 10.1186/s13256-022-03263-4 -
Journal of the American Society of... Jun 2022
Topics: Acute Kidney Injury; Humans; Tumor Lysis Syndrome; Uric Acid
PubMed: 35641305
DOI: 10.1681/ASN.2022040425 -
Journal of Medical Case Reports Jun 2022Tumor lysis syndrome is an oncologic emergency that involves multiple metabolic abnormalities and clinical symptoms such as acute renal failure, cardiac arrhythmias,... (Review)
Review
BACKGROUND
Tumor lysis syndrome is an oncologic emergency that involves multiple metabolic abnormalities and clinical symptoms such as acute renal failure, cardiac arrhythmias, seizures, and multiorgan failure, and may be fatal if not promptly recognized. Tumor lysis syndrome occurs most often in patients with hematologic malignancies, and relatively few cases have been described in patients with sarcoma.
CASE PRESENTATION
A 64-year-old male of Asian heritage presented to his primary care physician with a right lower-extremity mass and was ultimately diagnosed with widely metastatic osteosarcoma. He was treated with one cycle of cisplatin and doxorubicin that was complicated by hypervolemia and hypoxic respiratory failure. Given concerns for volume overload, therapy was changed to single-agent, dose-reduced ifosfamide. After receiving one dose of ifosfamide 1 g/m (1.8 g total) intravenously over 1 hour, the patient developed renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and lactic acidosis. The patient ultimately died from severe electrolyte abnormalities associated with tumor lysis syndrome.
CONCLUSION
This is the first instance of tumor lysis syndrome described in a patient with osteosarcoma undergoing ifosfamide monotherapy. Clinicians must be vigilant in identifying tumor lysis syndrome regardless of the malignancy type or chemotherapy regimen in order to prevent potentially fatal complications.
Topics: Bone Neoplasms; Cisplatin; Humans; Ifosfamide; Male; Middle Aged; Neoplasms, Second Primary; Osteosarcoma; Tumor Lysis Syndrome
PubMed: 35761364
DOI: 10.1186/s13256-022-03469-6 -
Journal of Medical Case Reports Mar 2017This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor. (Review)
Review
BACKGROUND
This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor.
CASE PRESENTATION
A 65-year-old white woman had tumor lysis syndrome, which represent a dangerous oncological emergency. This syndrome occurs usually with a hematological tumor, but in this case our patient had a solid tumor, which was a rare extraskeletal osteosarcoma, localized in her pelvic region. She also had lung metastases and bilateral hydronephrosis. After spontaneous tumor lysis syndrome, she had acute renal insufficiency, which was treated with hemodialysis and successively with rasburicase, Kayexalate (sodium polystyrene sulfonate), and febuxostat.
CONCLUSION
Tumor lysis syndrome represents an oncological emergency, which must be suspected and treated as soon as possible.
Topics: Abdominal Pain; Acute Kidney Injury; Aged; Antineoplastic Agents; Bone Neoplasms; Female; Gout Suppressants; Humans; Osteosarcoma; Peritoneal Neoplasms; Renal Dialysis; Treatment Outcome; Tumor Lysis Syndrome; Urate Oxidase
PubMed: 28335813
DOI: 10.1186/s13256-017-1241-3 -
The Oncologist Nov 2017Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening complication associated with the treatment of some cancers. If left untreated, TLS may result... (Review)
Review
UNLABELLED
Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B-cell lymphoma-2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control.
IMPLICATIONS FOR PRACTICE
Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.
Topics: Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Disease Management; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Proto-Oncogene Proteins c-bcl-2; Purines; Quinazolinones; Risk Factors; Sulfonamides; Tumor Burden; Tumor Lysis Syndrome
PubMed: 28851760
DOI: 10.1634/theoncologist.2017-0055