Purpose: Chimeric antigen receptor T-cell (CAR-T) therapy has been proven very effective in treating hematologic malignancies. Ciltacabtagene autoleucel (cilta-cel), a second-generation CAR-T cell with double B cell maturation antigen (BCMA) targeting binding domains, showed an 88% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (MM), which were carried out in our institute. This study aimed to assess the prognostic potential of soluble BCMA (sBCMA) in serum as a biomarker in MM after CAR-T therapy.

Patients And Methods: Serum samples (n = 44) from MM patients were collected before and after CAR-T therapy. The level of sBCMA was analyzed by enzyme-linked immunosorbent assay (ELISA). Additionally, three patients' long-term longitudinal analysis were performed.

Results: Serum sBCMA level was correlated with the percentage of malignant plasma cells in bone marrow (r = 0.613). After CAR-T infusion, the sBCMA level in serum of MM patients decreased markedly (median: 508,513 pg/mL before CAR-T infusion, 89,198 pg/mL in the first month, 8448 pg/mL in the second months, and 6010 pg/mL in the third month after CAR-T infusion). In patients who obtained objective response (≥ PR), re-elevated sBCMA indicated the possibility of disease recurrence. At a cutoff 69,326.27 pg/mL, sBCMA shows high sensitivity (87.5%) and specificity (88.5%) for identifying relapse of MM after CAR-T therapy.

Conclusion: Our results suggested that serum sBCMA level changes in response to the clinical status of MM patients after anti-BCMA CAR-T therapy. Furthermore, sBCMA may be a auxiliary biomarker for disease monitoring in MM patients after CAR-T therapy.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.retram.2023.103378DOI Listing

Publication Analysis

Top Keywords

car-t therapy
16
sbcma level
12
car-t infusion
12
car-t
10
soluble bcma
8
multiple myeloma
8
chimeric antigen
8
antigen receptor
8
receptor t-cell
8
sbcma
8

Similar Publications

Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments.

View Article and Find Full Text PDF

Cytokine screening identifies TNF to potentially enhance immunogenicity of pediatric sarcomas.

Front Immunol

December 2024

Department of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Introduction: Pediatric sarcomas, including osteosarcoma (OS), Ewing sarcoma (EwS) and rhabdomyosarcoma (RMS) carry low somatic mutational burden and low MHC-I expression, posing a challenge for T cell therapies. Our previous study showed that mediators of monocyte maturation sensitized the EwS cell line A673 to lysis by HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) transgenic CD8 T cells (CHM1 CD8 T cells).

Methods: In this study, we tested a panel of monocyte maturation cytokines for their ability to upregulate immunogenic cell surface markers on OS, EwS and RMS cell lines, using flow cytometry.

View Article and Find Full Text PDF

Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy Tumor Reactive T cell (TRT) Process has been developed.

View Article and Find Full Text PDF

This study explores a novel therapeutic strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL) by integrating autologous hematopoietic stem cell transplantation (ASCT) with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T cell therapy. A 20-year-old Asian male with refractory BL, whose lymphoma had not responded to multiple chemoimmunotherapy regimens, received myeloablative ASCT followed three days later by infusion of a novel third-generation CAR T cells engineered with CD28 and CD3ζ signaling domains, along with a TLR2 costimulatory domain. This resulted in sustained complete remission at the 306-day follow-up, without experiencing any severe complications.

View Article and Find Full Text PDF

Disease burden is a critical determinant of outcomes in CAR-T therapy for B-cell lymphomas, and one of the most widely used techniques for its assessment is Total Metabolic Tumor Volume (TMTV) measured via [F]FDG PET/CT. Biological parameters may further refine the risk profile. We analyzed baseline [F]FDG PET/CT scans from 40 patients treated with CAR-T, using an AI-based automated segmentation algorithm to determine TMTV.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!