Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia

Thomas, Xavier

doi:10.1080/14712598.2018.1533951

Cited by 8 publications

(6 citation statements)

References 99 publications

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“…Recent developments concerning other surface markers (CD22) could also be used in cases where CAR-T immunotherapy against CD19 does not work due to antigen loss. First clinical trials have shown promising results for patients with relapsed or refractory pre-B cell ALL [84,[87][88][89]. These results have met the needs and expectations of patients, physicians, scientists and investors, but it is important to remember that patients may not always respond to the therapy.…”

Section: Tisagenlecleucel Axicabtagene Ciloleucelmentioning

confidence: 99%

Genetically modified adoptive immunotherapy- new therapeutic option to cure relapsed and/or refractory leukemia in children and adults?

Reuther¹

2018

medical-oncology

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Refractory/relapsed leukemias in children, adolescents and adults are generally associated with a poor prognosis and usually require allogeneic stem cell transplantation. Despite the significant developments over the past few decades, a reliable therapy leading to long-term complete remission is still not available. Therefore, the development of adoptive immunotherapies has gained enormous importance. In recent years various leukemia-specific antibodies have been established for treatment of relapsed and/or refractory leukemias. Checkpoint inhibitors have provided significant progress in the therapy of various relapsed/refractory/metastatic tumor entities, but were not successful in highrisk leukemias. A recent milestone in the development of new specific treatment for relapsed/ refractory leukemias are genetically engineered T cells expressing a Chimeric Antigen Receptor that targets specific antigens (CAR-T cells). These CAR-T cells represent a combination of gene and immunotherapy with impressive results in the treatment of pediatric and young adult patients with aggressive acute lymphoblastic leukemia or diffuse large B-cell lymphoma and in the treatment of adults with primary mediastinal B-cell lymphoma. This review summarizes the current possibilities of adoptive immunotherapies, with a focus on leukemias and the situation in Germany.

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Section: Tisagenlecleucel Axicabtagene Ciloleucelmentioning

confidence: 99%

Genetically modified adoptive immunotherapy- new therapeutic option to cure relapsed and/or refractory leukemia in children and adults?

Reuther¹

2018

medical-oncology

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“…1 The groundbreaking work of Farber and Diamond 2 demonstrated that folic acid antagonists can induce temporary remissions in ALL, paving the way for chemotherapy as the primary treatment for ALL. Despite the advancements in alternative treatment strategies over the years, 3,4 chemotherapy remains the preferred approach for managing childhood ALL. The standard chemotherapy treatment typically comprises 3 phases lasting approximately 2-2.5 years: remission induction, consolidation (or intensification) and maintenance (or continuation).…”

Section: Introductionmentioning

confidence: 99%

A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase‐based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia

Yin,

Cheng,

Yang

et al. 2023

Brit J Clinical Pharma

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AimsMethotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT‐based hepatotoxicity remains unclear. This study aimed to develop a semi‐mechanistic PK/pharmacodynamic (PD) model to characterize the MTX‐induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukemia.MethodsA retrospective study was conducted on paediatric patients who received high‐dose (3‐5 g/m2) MTX treatment. MTX concentrations were assessed at 24‐hour intervals until the concentration dropped below 0.1 μmol/L. ALT concentrations were measured both before and after MTX administration. A population PK model was initially developed, which was later connected to a semi‐mechanistic hepatotoxicity model.ResultsThe PK model was developed using 354 MTX concentrations obtained from 51 patients, while the PD model was constructed using 379 ALT concentrations collected from 48 patients. The optimal PK model for MTX consisted of a two‐compartment structure, where body surface area served as a covariate for clearance and central volume of distribution. An indirect response model coupled to a liver injury signal transduction model was developed to describe the dynamics of ALT after MTX administration. The drug effect was adequately described by a linear model, exhibiting considerable inter‐occasion variability for each treatment session. No significant covariates were identified to have an impact on the PD parameters.ConclusionA semi‐mechanistic model was developed to describe ALT‐based hepatotoxicity of MTX, and it has the potential to serve as a valuable tool for characterizing drug‐induced hepatotoxicity.

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“…Another promising immunotherapy is chimeric antigen receptor (CAR) T-cell treatment, which uses gene transfer technology to develop a patient's cytotoxic T cells that consistently make CARs [12]. CAR T-cell treatment targeting CD19 [13] and CD20 has shown great potential in the therapy of malignant tumors of the B-cell type; acute lymphocytic leukemia (ALL) is one example [14,15], as is non-Hodgkin lymphoma (NHL) [14]. Boosting the immune system, despite the promise of clinical findings of cancer immunotherapy in certain malignancies, separates from the regular side effects of standard cancer treatments; immune-related adverse events (irAEs) produce immune-related adverse effects, which are a subset of inflammatory toxicities (irAEs) [16].…”

Section: Introductionmentioning

confidence: 99%

Emerging Management Approach for the Adverse Events of Immunotherapy of Cancer

et al. 2022

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Immunotherapy, which stimulates the body’s immune system, has received a considerable amount of press in recent years because of its powerful benefits. Cancer immunotherapy has shown long-term results in patients with advanced disease that are not seen with traditional chemotherapy. Immune checkpoint inhibitors, cytokines like interleukin 2 (IL-2) and interferon-alpha (IFN), and the cancer vaccine sipuleucel-T have all been licensed and approved by the FDA for the treatment of various cancers. These immunotherapy treatments boost anticancer responses by stimulating the immune system. As a result, they have the potential to cause serious, even fatal, inflammatory and immune-related side effects in one or more organs. Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell therapy are two immunotherapy treatments that are increasingly being used to treat cancer. Following their widespread usage in the clinic, a wave of immune-related adverse events (irAEs) impacting virtually every system has raised concerns about their unpredictability and randomness. Despite the fact that the majority of adverse effects are minimal and should be addressed with prudence, the risk of life-threatening complications exists. Although most adverse events are small and should be treated with caution, the risk of life-threatening toxicities should not be underestimated, especially given the subtle and unusual indications that make early detection even more difficult. Treatment for these issues is difficult and necessitates a multidisciplinary approach involving not only oncologists but also other internal medicine doctors to guarantee quick diagnosis and treatment. This study’s purpose is to give a fundamental overview of immunotherapy and cancer-related side effect management strategies.

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Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia

Cited by 8 publications

References 99 publications

Genetically modified adoptive immunotherapy- new therapeutic option to cure relapsed and/or refractory leukemia in children and adults?

Genetically modified adoptive immunotherapy- new therapeutic option to cure relapsed and/or refractory leukemia in children and adults?

A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase‐based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia

Emerging Management Approach for the Adverse Events of Immunotherapy of Cancer

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