Publications by authors named "R T Verona"

Introduction: Teclistamab, the first approved B-cell maturation antigen-directed bispecific antibody for treatment of triple-class exposed relapsed/refractory multiple myeloma, demonstrated deep, durable responses with a manageable safety profile in the pivotal MajesTEC-1 cohort (NCT03145181/NCT04557098). Efficacy, safety, and pharmacokinetics from the MajesTEC-1 China cohort are reported.

Methods: Patients received teclistamab 1.

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Article Synopsis
  • Teclistamab is a bispecific antibody approved for treating patients with relapsed/refractory multiple myeloma who have previously undergone multiple treatments, including BCMA-targeted therapies.
  • In a clinical study (MajesTEC-1), patients with a median of six prior treatments received weekly doses of teclistamab, resulting in a 52.5% overall response rate with some achieving complete remission.
  • The treatment had manageable side effects, with common adverse events including neutropenia and infections, while showing a median overall survival of 15.5 months in heavily pretreated patients.
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Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC-1 study. Cytokines, especially interleukin (IL)-6, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL-6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5).

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Article Synopsis
  • Bispecific antibodies teclistamab and talquetamab show effectiveness against multiple myeloma, but their mechanisms of resistance remain unclear.
  • In laboratory studies on patients' bone marrow samples, the success of these treatments was linked to the balance of T cells and regulatory T cells in the samples.
  • Resistance to BsAb treatment indicates issues like low ratios of T-cells to myeloma cells and immunosuppression from Tregs, which hinder T-cell activity and reduce treatment efficacy.
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Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (R/RMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression. We correlated tumor characteristics and baseline immune profiles with clinical response and disease burden in patients with R/RMM from the pivotal phase 1/2 MajesTEC-1 study, focusing on patients treated with 1.

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