Dataset Information

Dual Targeting with CAR T Cells to Limit Antigen Escape in Multiple Myeloma.

ABSTRACT: Adoptive T-cell therapy targeting a single tumor antigen can induce remissions of hematologic cancers but relapses often occur due to the outgrowth of tumor cells with absent or low expression of the antigen. Strategies to simultaneousy target multiple antigens are needed to fully capitalize on the promise of this therapeutic strategy. In this issue of Blood Cancer Discovery, Fernández de Larrea and colleagues demonstrate in preclinical models of multiple myeloma that targeting BCMA and GPRC5D simultaneously with T cells engineered to express chimeric antigen receptors specific for these antigens may prevent tumor cell escape. See related article by Fernández de Larrea et al., p. 146.

SUBMITTER: Simon S

PROVIDER: S-EPMC8447280 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Dual Targeting with CAR T Cells to Limit Antigen Escape in Multiple Myeloma.

Simon Sylvain S Riddell Stanley R SR

Blood cancer discovery 20200803 2

Adoptive T-cell therapy targeting a single tumor antigen can induce remissions of hematologic cancers but relapses often occur due to the outgrowth of tumor cells with absent or low expression of the antigen. Strategies to simultaneousy target multiple antigens are needed to fully capitalize on the promise of this therapeutic strategy. In this issue of <i>Blood Cancer Discovery</i>, Fernández de Larrea and colleagues demonstrate in preclinical models of multiple myeloma that targeting BCMA and G ...[more]

PMID: 34661143

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Project description:ImportancePatients with high-risk newly diagnosed multiple myeloma (NDMM) often have poor outcomes with standard treatments, necessitating novel effective frontline therapies to enhance clinical outcomes. GC012F, a B-cell maturation antigen/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy, has been developed on the novel FasTCAR platform. Notably, its use as a frontline therapy for patients with high-risk NDMM who are eligible for transplant has not been thoroughly explored.ObjectiveTo examine the safety, pharmacokinetics, and patient health and survival outcomes associated with GC012F in individuals with NDMM.Design, setting, and participantsPatients were enrolled in this single-arm, open-label phase 1 cohort study between June 28, 2021, and June 1, 2023 (the data cutoff date). All patients included in this study were treated at a single center, Shanghai Changzheng Hospital. The patients in the efficacy evaluation were followed up for a minimum period of 3 months.InterventionPatients underwent 2 cycles of induction therapy, followed by GC012F infusion (at 1 × 105 cells/kg, 2 × 105 cells/kg, or 3 × 105 cells/kg).Main outcomes and measuresThe primary goals were to assess the safety, efficacy, and pharmacokinetics of GC012F at various dose levels.ResultsOf 22 patients receiving GC012F treatment, 6 experienced mild to moderate cytokine release syndrome (grade 1-2) and none experienced neurotoxic effects. Nineteen patients were included in the efficacy evaluation, and all 19 patients showed stringent complete responses and achieved minimal residual disease negativity. The treatment's effectiveness was consistent across different dose levels. GC012F demonstrated a rapid response, with a median time to first stringent complete response of 84 days (range, 26-267 days) and achieving minimal residual disease negativity within 28 days (range, 23-135 days). The CAR T-cell expansion was robust, with a median peak copy number of 60 652 copies/μg genomic DNA (range, 8754-331 159 copies/μg genomic DNA), and the median time to median peak copy number was 10 days (range, 9-14 days).Conclusions and relevanceThe findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed.

Dataset Information

Dual Targeting with CAR T Cells to Limit Antigen Escape in Multiple Myeloma.

Publications

Dual Targeting with CAR T Cells to Limit Antigen Escape in Multiple Myeloma.

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