T-cell Therapy Research Articles

A multi-scale semi-mechanistic CK/PD model for CAR T-cell therapy

A multi-scale semi-mechanistic CK/PD model for CAR T-cell therapy

New Study Sheds Light on Secondary Cancer Risk After CAR T-Cell Therapy

New Study Sheds Light on Secondary Cancer Risk After CAR T-Cell Therapy

Costs, challenges and opportunities of decentralised chimeric antigen receptor T-cell production: a literature review and clinical experts’ interviews

The objectives were to summarise the evidence and clinical experts’ views comparing the use of decentralised produced chimeric antigen receptor (CAR) T-cell therapies versus commercially available products, regarding drug costs,...

The occurrence of cytokine release syndrome and its impact on the prognosis of patients with relapsed and refractory multiple myeloma following chimeric antigen receptor T-cell therapy

Objective: To analyze the incidence of cytokine release syndrome (CRS) and its impact on the prognosis of patients with relapsed and refractory multiple myeloma (RRMM) following treatment with chimeric antigen receptor T-cell (CAR-T) therapy. Methods: A retrospective collection was conducted of the clinical data of 91 patients with RRMM who underwent CAR-T therapy at the Affiliated Hospital of Xuzhou Medical University from January 2020 to October 2022. Before CAR-T cell infusion, the patient underwent pretreatment with the fludarabine plus cyclophosphamide (FC) regimen. On day 0 (d0), the patient received a dose of 1×106 cells/kg of CAR-T. The occurrence of CRS was recorded post-treatment and graded accordingly, with grades 1 to 2 indicating mild CRS and grade≥3 indicating severe CRS. The follow-up cut-off date was February 14, 2023, with a median follow-up time [M (Q1, Q3)] of 14.1 (3.1, 37.7) months. Kaplan-Meier survival curve analysis assessed the progression-free survival (PFS) and overall survival (OS) of Grade 1 and Grade 2 CRS patients. Furthermore, univariate logistic regression analysis was conducted to identify factors associated with the development of severe CRS. Results: In a cohort of 91 patients diagnosed with RRMM, there were 51 male and 40 female individuals, with a median age [M (Q1,Q3)] of 57 (31, 73) years. All 91 cases (100%) experienced CRS, with 82 cases (90%) classified as mild (grades 1-2) CRS and 9 cases (10%) classified as severe (grades 3-5) CRS. In a study involving 9 patients with severe CRS, 8 cases resulted in mortality. The Kaplan-Meier survival curve analysis revealed that among grade 1 CRS patients, neither the median PFS nor the median OS was achieved. For grade 2 CRS patients, the median PFS was 12 months (95%CI: 4-not achieved), and the median OS was 21 months (95%CI: 4-not achieved). The progression-free survival and overall survival rates of grade 2 CRS patients were both lower than those of grade 1 CRS patients (both P<0.05). Single-factor logistic regression analysis revealed that a high tumor burden (OR=1.025, 95%CI: 1.002-1.049, P=0.031), a prolonged duration of CRS onset (OR=0.809, 95%CI: 0.646-0.971, P=0.037) and persistence (OR=1.758, 95%CI: 1.349-2.481, P=0.001) were identified as significant factors associated with severe CRS in patients with RRMM. Conclusions: Patients with RRMM who undergoes CAR-T therapy have a high incidence of CRS, with a higher mortality rate among those experiencing severe CRS. Furthermore, patients with grade 2 CRS exhibit lower rates of progression-free survival and overall survival compared to those with grade 1 CRS. Factors associated with the development of severe CRS in RRMM patients include high tumor burden and prolonged duration and onset of CRS.

Safety and efficacy of B cell maturation antigen-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma and concurrent light chain amyloidosis.

Clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma (RRMM) have typically excluded patients with AL amyloidosis. As a result, there are limited data on the safety and efficacy of CAR T-cell therapy in this patient population. We retrospectively reviewed eight consecutive patients with RRMM and AL amyloidosis who were treated with standard of care CAR T-cell therapy. Cytokine release syndrome was seen in 75% of patients (grade ≥3: 0%) and immune effector cell-associated neurotoxicity syndrome (grade 1) in only one patient. Low-grade cytopenias were common (any grade/grade ≥3: neutropenia 62.5%/37.5%, anemia 37.5%/0%, thrombocytopenia 25%/0%). CAR T-cell therapy led to rapid and deep responses with a median time to best response of 43 days and a hematologic very good partial response or better rate of 62.5%. Overall, we found that commercial CAR T-cell therapy was feasible, and effective in patients with RRMM and concurrent AL amyloidosis.

Current Insights into CAR T-Cell-Based Therapies for Myelodysplastic Syndrome.

Myelodysplastic syndromes (MDS) are due to defective hematopoiesis in bone marrow characterized by cytopenia and dysplasia of blood cells, with a varying degree of risk of acute myeloid leukemia (AML). Currently, the only potentially curative strategy is hematopoietic stem cell transplantation (HSCT). Many patients are ineligible for HSCT, due to late diagnosis, presence of co-morbidities, old age and complications likely due to graft-versus-host disease (GvHD). As a consequence, patients with MDS are often treated conservatively with blood transfusions, chemotherapy, immunotherapy etc. based on the grade and manifestations of MDS. The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized immunotherapy for hematological malignancies, as evidenced by a large body of literature. However, resistance and toxicity associated with it are also a challenge. Hence, there is an urgent need to develop new strategies for immunological and hematopoetic management of MDS. Herein, we discuss current limitations of CAR T-cell therapy and summarize novel approaches to mitigate this. Further, we discuss the in vivo activation of tumor-specific T cells, immune check inhibitors (ICI) and other approaches to normalize the bone marrow milieu for the management of MDS.

Real-World Treatment Patterns and Outcomes of Patients with Large B-cell Lymphoma (LBCL) Who Received Loncastuximab Tesirine Prior to Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Real-World Treatment Patterns and Outcomes of Patients with Large B-cell Lymphoma (LBCL) Who Received Loncastuximab Tesirine Prior to Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Tumor's Digest: Macrophage Metabolism Creates a Barrier to T Cells.

Changes in the composition and physical properties of the tumor extracellular matrix are linked to poor cytotoxic T-cell infiltration and therapy response, yet the underlying mechanisms remain unclear. Tharp and colleagues revealed a fascinating cascade where tumor fibrosis alters macrophage metabolism, restricting the nutrients available to infiltrating T cells and resulting in their suppression and exclusion from the tumor microenvironment. This study suggests that targeting metabolic pathways could be a promising strategy to overcome the immune suppression induced by the tumor extracellular matrix.

ABCL-368 Real-world Treatment Patterns and Outcomes of Patients with Large B-cell Lymphoma (LBCL) Who Received Loncastuximab Tesirine Prior to Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

ABCL-368 Real-world Treatment Patterns and Outcomes of Patients with Large B-cell Lymphoma (LBCL) Who Received Loncastuximab Tesirine Prior to Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Glofitamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma: Extended Follow-Up from a Pivotal Phase 2 Study and Subgroup Analyses in Patients with Prior Chimeric Antigen Receptor T-Cell Therapy and by Baseline Total Metabolic Tumor Volume

Glofitamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma: Extended Follow-Up from a Pivotal Phase 2 Study and Subgroup Analyses in Patients with Prior Chimeric Antigen Receptor T-Cell Therapy and by Baseline Total Metabolic Tumor Volume

National Trends in the Utilization of Chimeric Antigen Receptor T-Cell Therapy: The Real-World Story Since Its Approval

National Trends in the Utilization of Chimeric Antigen Receptor T-Cell Therapy: The Real-World Story Since Its Approval

CT-219 Clinical Evaluation of Fast-in-Time (FIT) Anti-CD19 CAR T—a Non-Viral, 2-Day Rapid Manufacture CAR T-Cell Therapy for B-Cell Malignancies

CT-219 Clinical Evaluation of Fast-in-Time (FIT) Anti-CD19 CAR T—a Non-Viral, 2-Day Rapid Manufacture CAR T-Cell Therapy for B-Cell Malignancies

Safety and Efficacy of 9 Days Vein-to-Vein Decentralized Manufactured Anti-CD19 CAR T-Cell Therapy for Relapsed/Refractory B-cell Leukemia and Lymphoma: Results from the First Phase 1 Indian Trial (VELCART)

Safety and Efficacy of 9 Days Vein-to-Vein Decentralized Manufactured Anti-CD19 CAR T-Cell Therapy for Relapsed/Refractory B-cell Leukemia and Lymphoma: Results from the First Phase 1 Indian Trial (VELCART)

CT-165 Safety and Efficacy of 9 Days Veinto-Vein Decentralized Manufactured Anti-CD19 CAR T-Cell Therapy for Relapsed/Refractory B-cell Leukemia and Lymphoma: Results from the First Phase 1 Indian Trial (VELCART)

CT-165 Safety and Efficacy of 9 Days Veinto-Vein Decentralized Manufactured Anti-CD19 CAR T-Cell Therapy for Relapsed/Refractory B-cell Leukemia and Lymphoma: Results from the First Phase 1 Indian Trial (VELCART)

ABCL-370 Real-World Clinical Effectiveness of Loncastuximab Tesirine Monotherapy for the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma Following Chimeric Antigen T-Cell Therapy in the US

ABCL-370 Real-World Clinical Effectiveness of Loncastuximab Tesirine Monotherapy for the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma Following Chimeric Antigen T-Cell Therapy in the US

Combination of Pirtobrutinib and Lentiviral Transduced Bispecific Anti-CD20/CD19 (LV20 .19) CAR T-Cell Therapy to Improve Outcomes in Patients With Relapsed/Refractory Lymphoma

Combination of Pirtobrutinib and Lentiviral Transduced Bispecific Anti-CD20/CD19 (LV20 .19) CAR T-Cell Therapy to Improve Outcomes in Patients With Relapsed/Refractory Lymphoma

ABCL-720 Combination of Pirtobrutinib and Lentiviral Transduced Bispecific Anti-CD20/CD19 (LV20.19) CAR T-Cell Therapy to Improve Outcomes in Patients With Relapsed/Refractory Lymphoma

ABCL-720 Combination of Pirtobrutinib and Lentiviral Transduced Bispecific Anti-CD20/CD19 (LV20.19) CAR T-Cell Therapy to Improve Outcomes in Patients With Relapsed/Refractory Lymphoma

CARs Moving Forward: The Development of CAR T-Cell Therapy in the Earlier Treatment Course of Hematologic Malignancies

Chimeric antigen receptor T-cell (CAR-T) has revolutionized the treatment of hematologic malignancies. There are several approvals in lymphomas, leukemias and myeloma. Randomized clinical trials have shown that CAR-T cell therapy improves survival over standard of care in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM), changing dramatically the current treatment paradigm. Current efforts are directed in improving outcomes in the frontline setting and confirmatory randomized trials are ongoing.

Novel CAR-T Cells Specifically Targeting SIA-CIgG Demonstrate Effective Antitumor Efficacy in Bladder Cancer.

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising cancer treatment method. However, its application in bladder cancer (BC) remains limited, partially because of the absence of appropriate target molecules. Sialylated cancer-derived IgG (SIA-CIgG) is highly expressed in BC and is closely associated with malignant biological behavior. However, its potential as a target for CAR-T cell therapy to treat BC is yet to be established. Here, it is found that SIA-CIgG is highly expressed in most BC samples but displayed limited expression in normal tissues. CAR-T cells specifically targeting SIA-CIgG can effectively lyse BC cells and the cytotoxicity depends on SIA-CIgG expression. Furthermore, SIA-CIgG CAR-T cells demonstrate milder tumor cell lysis and enhanced persistence compared with human epidermal growth factor receptor 2 (HER2) CAR-T cells, which have undergone extensive clinical trials. After repeated tumor antigen challenges, SIA-CIgG CAR-T cells display substantial alterations in both the transcriptome and chromatin accessibility. When combining SIA-CIgG CAR-T cell therapy with FDA-approved drugs to treat BC, the histone deacetylase inhibitor (HDACi), vorinostat, is found to enhance the ablility of CAR-T cells for tumor cell lysis. Therefore, the combination of SIA-CIgG CAR-T cells and vorinostat is promising for BC treatment.

Outcome of patients with large B-cell lymphoma treated with tafasitamab plus lenalidomide either before or after CAR T-cell therapy

AbstractTafasitamab plus lenalidomide (TAFA-LEN) treatment relevance pre- or post-anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is debated. We analyzed patients with large B-cell lymphoma in the DESCAR-T registry treated with axi[1]cel or tisa-cel in ≥3rd line and TAFA-LEN before (n = 15, “TL-pre-CAR-T” set) or directly after (n = 52, “TL-post-CAR-T” set) CAR T-cell therapy. We compared TAFA-LEN v. other treatments using inverse probability weighting in the TL-post-CAR[1]T set. In the TL-post-CAR-T set, the median progression-free survival (mPFS), overall survival (mOS), and duration of response (mDOR) since the first treatment for progression (mPFS2/mOS2/mDOR2) were 3, 4.7, and 8.1 months, respectively. The best overall response rate (bORR) and best complete response rate (bCRR) after TAFA-LEN were 13.5% and 7.7%, respectively. Outcomes were better for patients who relapsed >6 months after CAR T-cell therapy (mPFS2: 5.6 vs 2 months, P = .0138; mOS2: not reached vs 3.8 months, P = .0034). The bORR and bCRR between TAFA-LEN and other treatments were 20.6% vs 24.9% and 11.6% vs 15.6%, respectively. Outcomes were similar between TAFA-LEN and other treatments (mPFS2: 2.9 vs 2.4 months, P = .91; mOS2: 3.3 vs 5.5 months, P = .06). In an exploratory analysis of the TL-pre-CAR-T set, the median TAFA-LEN treatment duration before CAR-T was 3.7 months with no patient becoming CD19 negative. The bORR, bCRR, 6- month PFS, and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1%, and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatment improved outcomes for patients relapsing after CAR T-cell therapy.