A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma

Atrash, Shebli; Moyo, Tamara K.

doi:10.2147/ott.s242018

Cited by 9 publications

(5 citation statements)

References 106 publications

(59 reference statements)

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“…Anti-CD30 CAR-T cells therapies have demonstrated significant clinical responses in early clinical trials of patients with B-NHL ( Table 4 ) [ 290 , 291 ]. There are other ongoing clinical trials with different CD30 CAR-T cell constructs in R/R lymphomas addressing ways to improve outcome ( Table 4 ) (reviewed in [ 329 , 330 ]).…”

Section: Clinical Trials Of Novel Anti-taa Inhibitors In the Treatmen...mentioning

confidence: 99%

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Tannoury

Garnier

Susin

et al. 2022

Cancers

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Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders.

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Section: Clinical Trials Of Novel Anti-taa Inhibitors In the Treatmen...mentioning

confidence: 99%

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Tannoury

Garnier

Susin

et al. 2022

Cancers

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“…Chimeric antigen receptor T (CAR-T) therapy has been revolutionary in human cancer due to its potent and durable clinical responses ( 4 ). This kind of therapy is to modify the T cells of the patient in vitro with the specific CAR structure through various techniques, and then reinfuse them back into the patient’s body to better recognize and kill the patient’s tumor cells ( 5 , 6 ). T cells are immune cells in the human body that can fight against abnormal cells including tumor cells ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy

Dou,

Ren,

Qiu

et al. 2024

Front. Med.

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BackgroundChimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.PurposeThis study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.Data sources and methodsWe searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.ResultsA total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% P = 0.338 z = −2.369 (p = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: −617.21, 95% confidence interval (−1104.41, −130.01) I[2] = 0% P = 0.88 Z = 2.48 (P = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: −11.58, 95% confidence interval (−15.28, −7.88) I[2] = 0.0% P = 0.73 z = 6.14 (p < 0.00001)].ConclusionThe prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.

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“…In the phase 1 and 2 clinical study of tisagenlecleucel, CRS occurred in 58 of 75 patients (77%) and 35 of 75 patients (47%) were admitted to the intensive care unit for management of CRS [11]. CRS is a systemic inflammatory response observed after adoptive T-cell therapy [25]. It is triggered by activated T-cells releasing cytokines and chemokines, as do other immune cells such as monocytes, macrophages, and dendritic cells [26].…”

Section: Introductionmentioning

confidence: 99%

Price and Prejudice? The Value of Chimeric Antigen Receptor (CAR) T-Cell Therapy

Choi

Shin

Bae

2022

IJERPH

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Although chimeric antigen receptor (CAR) T-cell therapy has shown a high response rate in lymphoma patients, its cost-effectiveness is controversial due to the high price and uncertainty of the clinical evidence. In addition to the high acquisition cost of CAR T-cell therapy, procedure and facility cost increase the financial burden considering the frequency of adverse events such as cytokine release syndrome. In clinical research, relatively short follow-up periods were used compared to traditional cancer agents. In addition, head-to-head comparative effectiveness data are unavailable, which is an important factor when evaluating the cost-effectiveness of a new treatment. Additional evidence that will compensate for the uncertainty of existing clinical data is needed for full evaluation of long-term efficacy, safety, and comparative effectiveness

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A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma

Cited by 9 publications

References 106 publications

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy

Price and Prejudice? The Value of Chimeric Antigen Receptor (CAR) T-Cell Therapy

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